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Estimating COPD occurrence is perceived by the scientific community as a matter of increasing interest because of the worldwide diffusion of the disease.,We aimed to estimate COPD prevalence by using administrative databases from a city in central Italy for 2002-2006, improving both the sensitivity and the reliability of the estimate.,Multiple sources were used, integrating the hospital discharge register (HDR), clinical charts, spirometry and the cause-specific mortality register (CMR) in a longitudinal algorithm, to reduce underestimation of COPD prevalence.,Prevalence was also estimated on the basis of COPD cases confirmed through spirometry, to correct misclassification.,Estimating such prevalence relied on using coefficients of validation, derived as the positive predictive value (PPV) for being an actual COPD case from clinical and spirometric data at the Institute of Clinical Physiology of the National Research Council.,We found that sensitivity of COPD prevalence increased by 37%.,The highest estimate (4.43 per 100 residents) was observed in the 5-year period, using a 3-year longitudinal approach and combined data from three sources.,We found that 17% of COPD cases were misclassified.,The above estimate of COPD prevalence decreased (3.66 per 100 residents) when coefficients of validation were applied.,The PPV was 80% for the HDR, 82% for clinical diagnoses and 91% for the CMR.,Adjusting the COPD prevalence for both underestimation and misclassification of the cases makes administrative data more reliable for epidemiological purposes. | Chronic obstructive pulmonary disease (COPD) is a known risk factor for lung cancer and a leading cause of mortality in the U.S., but its impact may not be fully appreciated, especially among low-income populations in the southeast where COPD prevalence and lung cancer incidence are elevated.,We conducted a prospective study among 26,927 low-income adults age 40-79 in the Southern Community Cohort Study who had a Center for Medicare and Medicaid Services (CMS) encounter prior to enrollment and were followed for a median of over 6 years.,Using a validated algorithm for assessing COPD from CMS claims data, we estimated COPD prevalence and potential misreporting.,From Cox proportional hazard models, we computed overall and lung cancer-specific mortality according to COPD status.,The overall prevalence of CMS-diagnosed COPD was 16%, but was twice as high among whites as blacks.,Only 35% of these individuals, however, self-reported having COPD, with underreporting significantly greater for blacks than whites.,Smoking-adjusted all-cause mortality was increased by 1.7-fold and lung cancer mortality by 2.3-fold among those with a CMS COPD diagnosis, with similar patterns in blacks and whites, but no excess was found among those self-reporting COPD and without CMS confirmation.,The prevalence of COPD in this low-income population may be greater than previously recognized and misreporting is common.,COPD is associated with elevated lung cancer mortality, even among those not self-reporting the condition. | 1 |
Blood eosinophil counts and history of exacerbations have been proposed as predictors of patients with chronic obstructive pulmonary disease (COPD) who may benefit from triple therapy (inhaled corticosteroid, long-acting β2-agonist and long-acting muscarinic antagonist).,In a retrospective cohort analysis we examined the profiles of COPD patients from the UK Clinical Practice Research Datalink (CPRD) and US Optum Clinformatics™ Data Mart (Optum) databases with reference to exacerbation frequency and blood eosinophil distribution.,Of the 31,437 (CPRD) and 383,825 (Optum) patients with COPD, 15,364 (CPRD) and 139,465 (Optum) met the eligibility criteria and were included.,Among patients with ≥2 exacerbations and available eosinophil counts in the baseline period (CPRD, n = 3089 and Optum, n = 13414), 17.0 and 13.3% respectively had eosinophil counts ≥400 cells/μL.,Patients with ≥2 exacerbations or eosinophil count ≥400 cells/μL during first year, exacerbated at least once (CPRD, 82.8% vs Optum, 80.6%) or continued to have eosinophil count ≥300 cells/μL (76.8% vs 76.5%), respectively in the follow-up year.,In both years, a higher variability in the number of exacerbations and eosinophil count was observed in patients with one exacerbation and eosinophil counts between 300 and 400 cells/μL; patients with eosinophil count < 150 cells/μL had the lowest variability.,Approximately 10% patients had both ≥2 exacerbations and eosinophil count ≥300 cells/μL across the databases.,A high variability in blood eosinophil counts over two consecutive years was observed in UK and US patients with COPD and should be considered while making treatment decisions.,A small proportion of COPD patients had frequent exacerbations and eosinophil count ≥300 cells/μL.,The online version of this article (10.1186/s12931-019-1130-y) contains supplementary material, which is available to authorized users. | This study aimed to measure the true burden of COPD by calculating incremental direct and indirect costs.,Direct medical resource use, productivity metrics, and COPD-specific resource use and costs were also evaluated.,This was a retrospective, observational, matched cohort study using administrative claims data from the Truven Health MarketScan® Commercial Claims and Encounters and the Health and Productivity Management databases (2007-2010).,Working-age (18-65 years) patients with COPD were identified as having at least one hospitalization or one emergency department visit or two outpatient visits.,Patients in the non-COPD cohort did not have a diagnosis of COPD during the study period.,Outcomes were evaluated in the first full calendar year after the year of identification (index).,Of the 5,701 patients with COPD identified, 3.6% patients were frequent exacerbators (≥2), 10.4% patients were infrequent exacerbators (1), and 86% patients were non-exacerbators (0).,When compared with the 17,103 patients without COPD, the incremental direct cost of COPD was estimated at $6,246/patient/year (95% confidence interval: $4,620, $8,623; P<0.001).,Loss in productivity was significantly greater in patients with COPD, with an average of 5 more days/year of absence from work and incremental indirect costs from short-term disability of $641 (P<0.001).,Direct costs for frequent exacerbators ($17,651/year) and infrequent exacerbators ($14,501/year) were significantly higher than those for non-exacerbators ($11,395, P<0.001).,Working-age patients with COPD incur statistically significantly higher direct and indirect costs and use more resources compared with those who do not have COPD. | 1 |
The prevalence of disabilities is rising steadily, reflecting an aging population and an increasing burden of chronic conditions affecting quality of life.,There are scant national data on the prevalence of disability among individuals with chronic obstructive pulmonary disease (COPD).,The main objective was to estimate the prevalence of common disabilities among US-based individuals diagnosed with COPD.,Data from the BRFSS, a national telephone survey examining health-related behaviors in 2016-2017 were analyzed.,The study population consisted of individuals with self-reported COPD (N = 38352 in 2016 and N = 35423 in 2017).,The prevalence of disabilities in hearing, vision, cognition, mobility, and independent living were obtained and adjusted with sampling weights.,Healthcare access measures were described by type of disability.,Mobility disability had the highest prevalence of 45.9 (44.8-47.0) % in 2016 and 48.4 (47.3-49.5) % in 2017 among respondents with COPD.,The prevalence of disabilities was highest among those 45-64 years old, except for hearing and cognition.,Hearing disabilities were most prevalent among males with COPD while cognitive and mobility disabilities were most prevalent among females with COPD.,While differences in the prevalence of disabilities were observed, access to health care was similar by disability type and age group among respondents.,Contrary to expectation, the highest prevalence of disabilities was found not to be among those 65 years old and above.,Further research is needed to explain this age-specific shift in the burden of disability, as long-term care planning and prevention support systems should be informed by the demographical patterns of disabilities among individuals with COPD. | Caregivers of individuals with COPD have a key role in maintaining patient adherence and optimizing patient function.,However, no systematic review has examined how the caregiver role has been operationalized in interventions to improve outcomes of individuals with COPD or the quality or effectiveness of these interventions.,The aims of this review were to 1) determine whether caregivers have been involved as part of interventions to improve outcomes of individuals with COPD; 2) determine the risk of bias within included intervention studies; and 3) examine the effectiveness of interventions that have involved caregivers in improving outcomes of individuals with COPD.,The electronic databases of Medline, Embase, PsycINFO, and Cochrane Library were searched from January 2000 to November 2015.,Experimental studies testing interventions that involved a caregiver to improve COPD patient outcomes were eligible.,Nine studies involving caregivers met inclusion criteria.,No studies reported any intervention components targeted solely at caregivers, with most instead including caregivers in dyadic or group education sessions about COPD delivered by health care professionals.,The risk of bias identified in included studies was mixed.,Seven of the nine studies were effective in improving a broad range of outcomes.,These findings highlight that there is an urgent need for methodologically rigorous interventions to examine the effectiveness of strategies to assist caregivers to provide direct care, encourage adherence to health care provider recommendations, act as a health care advocate, and provide emotional and psychosocial support to individuals with COPD. | 1 |
Functional activities, such as the sit-to-stand-to-sit (STSTS) task, are often impaired in individuals with chronic obstructive pulmonary disease (COPD).,The STSTS task places a high demand on the postural control system, which has been shown to be impaired in individuals with COPD.,It remains unknown whether postural control deficits contribute to the decreased STSTS performance in individuals with COPD.,Center of pressure displacement was determined in 18 individuals with COPD and 18 age/gender-matched controls during five consecutive STSTS movements with vision occluded.,The total duration, as well as the duration of each sit, sit-to-stand, stand and stand-to-sit phase was recorded.,Individuals with COPD needed significantly more time to perform five consecutive STSTS movements compared to healthy controls (19±6 vs. 13±4 seconds, respectively; p = 0.001).,The COPD group exhibited a significantly longer stand phase (p = 0.028) and stand-to-sit phase (p = 0.001) compared to the control group.,In contrast, the duration of the sit phase (p = 0.766) and sit-to-stand phase (p = 0.999) was not different between groups.,Compared to healthy individuals, individuals with COPD needed significantly more time to complete those phases of the STSTS task that require the greatest postural control.,These findings support the proposition that suboptimal postural control is an important contributor to the decreased STSTS performance in individuals with COPD. | Balance deficits are identified as important risk factors for falling in individuals with chronic obstructive pulmonary disease (COPD).,However, the specific use of proprioception, which is of primary importance during balance control, has not been studied in individuals with COPD.,The objective was to determine the specific proprioceptive control strategy during postural balance in individuals with COPD and healthy controls, and to assess whether this was related to inspiratory muscle weakness.,Center of pressure displacement was determined in 20 individuals with COPD and 20 age/gender-matched controls during upright stance on an unstable support surface without vision.,Ankle and back muscle vibration were applied to evaluate the relative contribution of different proprioceptive signals used in postural control.,Individuals with COPD showed an increased anterior-posterior body sway during upright stance (p = 0.037).,Compared to controls, individuals with COPD showed an increased posterior body sway during ankle muscle vibration (p = 0.047), decreased anterior body sway during back muscle vibration (p = 0.025), and increased posterior body sway during simultaneous ankle-muscle vibration (p = 0.002).,Individuals with COPD with the weakest inspiratory muscles showed the greatest reliance on ankle muscle input when compared to the stronger individuals with COPD (p = 0.037).,Individuals with COPD, especially those with inspiratory muscle weakness, increased their reliance on ankle muscle proprioceptive signals and decreased their reliance on back muscle proprioceptive signals during balance control, resulting in a decreased postural stability compared to healthy controls.,These proprioceptive changes may be due to an impaired postural contribution of the inspiratory muscles to trunk stability.,Further research is required to determine whether interventions such as proprioceptive training and inspiratory muscle training improve postural balance and reduce the fall risk in individuals with COPD. | 1 |
Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | Relationships between improvements in lung function and other clinical outcomes in chronic obstructive pulmonary disease (COPD) are not documented extensively.,We examined whether changes in trough forced expiratory volume in 1 second (FEV1) are correlated with changes in patient-reported outcomes.,Pooled data from three indacaterol studies (n = 3313) were analysed.,Means and responder rates for outcomes including change from baseline in Transition Dyspnoea Index (TDI), St.,George's Respiratory Questionnaire (SGRQ) scores (at 12, 26 and 52 weeks), and COPD exacerbation frequency (rate/year) were tabulated across categories of ΔFEV1.,Also, generalised linear modelling was performed adjusting for covariates such as baseline severity and inhaled corticosteroid use.,With increasing positive ΔFEV1, TDI and ΔSGRQ improved at all timepoints, exacerbation rate over the study duration declined (P < 0.001).,Individual-level correlations were 0.03-0.18, but cohort-level correlations were 0.79-0.95.,At 26 weeks, a 100 ml increase in FEV1 was associated with improved TDI (0.46 units), ΔSGRQ (1.3-1.9 points) and exacerbation rate (12% decrease).,Overall, adjustments for baseline covariates had little impact on the relationship between ΔFEV1 and outcomes.,These results suggest that larger improvements in FEV1 are likely to be associated with larger patient-reported benefits across a range of clinical outcomes.,ClinicalTrials.gov NCT00393458, NCT00463567, and NCT00624286 | 1 |
Growing evidence suggests that blood eosinophil count is associated with patient responsiveness to inhaled corticosteroids (ICS).,We performed post hoc predictive modeling on data from the FORWARD study and two replicate studies by Dransfield, to evaluate the relationships between baseline eosinophil count and the effect of ICS on exacerbations and lung function in patients with COPD.,The studies assessed ICS/long-acting β2 agonist (LABA) combinations vs LABA alone.,Using data from each study, we modeled COPD exacerbation rates, predose FEV1, and St George’s Respiratory Questionnaire score ([FORWARD only]) over a continuous range of eosinophils (0-1,000 eosinophils/µL in FORWARD, 0-993 eosinophils/µL in Dransfield).,In all studies, ICS/LABA reduced exacerbations versus LABA alone across all eosinophil levels, with progressively greater reductions at increasing baseline blood eosinophil counts.,In FORWARD, annual exacerbation rates ranged from 0.78 to 0.83 per year between 0 and 1,000 eosinophils/µL in the ICS/LABA arm, and from 0.81 to 1.54 per year in the LABA-only arm.,In the Dransfield studies, exacerbation rates ranged from 0.54 to 1.02 per year in the ICS/LABA arm between 0 and 993 eosinophils/µL, and from 0.56 to 1.75 per year in the LABA-only arm.,Change in FEV1 was not associated with eosinophil count in ICS-treated patients in FORWARD, whereas an increased treatment benefit in terms of FEV1 was observed at higher eosinophil levels in the Dransfield studies.,ICS/LABA led to greater improvements in St George’s Respiratory Questionnaire total scores compared to LABA alone in patients in FORWARD with ≥67 eosinophils/µL.,Higher blood eosinophil count in patients with COPD is associated with an increased beneficial effect from ICS in terms of exacerbation reduction.,Further prospective data are required to assess the role of blood eosinophils as a biomarker for therapeutic recommendations. | The landmark study of Fletcher and Peto on the natural history of tobacco smoke-related chronic airflow obstruction suggested that decline in the forced expiratory volume in the first second (FEV1) in chronic obstructive pulmonary disease (COPD) is slow at the beginning, becoming faster with more advanced disease.,The present authors reviewed spirometric data of COPD patients included in the placebo arms of recent clinical trials to assess the lung function decline of each stage, defined according to the severity of airflow obstruction as proposed by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.,In large COPD populations the mean rate of FEV1 decline in GOLD stages II and III is between 47 and 79 mL/year and 56 and 59 mL/year, respectively, and lower than 35 mL/year in GOLD stage IV.,Few data on FEV1 decline are available for GOLD stage I.,Hence, the loss of lung function, assessed as expiratory airflow reduction, seems more accelerated and therefore more relevant in the initial phases of COPD.,To have an impact on the natural history of COPD, it is logical to look at the effects of treatment in the earlier stages. | 1 |
Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide.,Patients with chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), are exposed to a higher risk of developing lung cancer.,Chronic inflammation may play an important role in the lung carcinogenesis among those patients.,The present study aimed at identifying candidate biomarker predicting lung cancer risk among patients with chronic respiratory diseases.,We applied clinical bioinformatics tools to analyze different gene profile datasets with a special focus on screening the potential biomarker during chronic inflammation-lung cancer transition.,Then we adopted an in vitro model based on LPS-challenged A549 cells to validate the biomarker through RNA-sequencing, quantitative real time polymerase chain reaction, and western blot analysis.,Bioinformatics analyses of the 16 enrolled GSE datasets from Gene Expression Omnibus online database showed myocyte enhancer factor 2D (MEF2D) level significantly increased in COPD patients coexisting non-small-cell lung carcinoma (NSCLC).,Inflammation challenge increased MEF2D expression in NSCLC cell line A549, associated with the severity of inflammation.,Extracellular signal-regulated protein kinase inhibition could reverse the up-regulation of MEF2D in inflammation-activated A549.,MEF2D played a critical role in NSCLC cell bio-behaviors, including proliferation, differentiation, and movement.,Inflammatory conditions led to increased MEF2D expression, which might further contribute to the development of lung cancer through influencing cancer microenvironment and cell bio-behaviors.,MEF2D might be a potential biomarker during chronic inflammation-lung cancer transition, predicting the risk of lung cancer among patients with chronic respiratory diseases.,The online version of this article (doi:10.1186/s12967-017-1168-x) contains supplementary material, which is available to authorized users. | Effects of pulmonary diseases [asthma, chronic obstructive pulmonary disease (COPD), and lung tuberculosis (TB)] on subsequent lung cancer development have been reported.,However, whether patients with coexisting pulmonary diseases are at greater risk of developing various histologic types of lung cancer remains elusive.,Patients newly diagnosed with lung cancer between 2004 and 2008 were identified from National Health Insurance Research Database (Taiwan).,The histologic types of lung cancer were further confirmed using Taiwan Cancer Registry Database.,Cox proportional hazard regression was used to calculate the hazard ratio (HR) of coexisting asthma, COPD and/or TB to estimate lung cancer risk by histologic type.,During the study period, 32,759 cases of lung cancer were identified from 15,219,024 residents age 20 years and older, who were free from the disease before 2003.,Coexisting pulmonary diseases showed stronger association with lung cancer than specific lung disorders.,Specifically, among men, the HRs for squamous cell carcinoma (SqCC) were 3.98 (95% CI, 3.22-4.93), 2.68 (95% CI, 2.45-2.93), and 2.57 (95% CI, 2.10-3.13) for individuals with asthma+COPD+TB, asthma+COPD, and COPD+TB, respectively.,Among women, the HRs for SqCC were 3.64 (95% CI, 1.88-7.05), 3.35 (95% CI, 1.59-7.07), and 2.21 (95% CI, 1.66-2.94) for individuals with TB, COPD+TB, and asthma+COPD, respectively.,Adenocarcinoma HRs for men and women were 2.00 (95% CI, 1.54-2.60) and 2.82 (95% CI, 1.97-4.04) for individuals with asthma+COPD+TB, 2.28 (95% CI, 1.91-2.73) and 2.16 (95% CI, 1.57-2.95) for COPD+TB, and 1.76 (95% CI, 1.04-2.97) and 2.04 (95% CI, 1.02-4.09) for individuals with asthma+TB.,Specifically, small cell carcinoma (SmCC) HRs among men were 3.65 (95% CI, 1.97-6.80), 2.20 (95% CI, 1.45-3.36), and 2.14 (95% CI, 1.86-2.47) for those with asthma+TB, asthma+COPD+TB, and asthma+ COPD, respectively.,Among women, the HRs of SmCC were 8.97 (95% CI, 3.31-24.28), 3.94 (95% CI, 1.25-12.35) and 3.33 (95% CI, 2.23-4.97) for those with asthma+COPD+TB, COPD+TB, and asthma+COPD, respectively.,Patients with coexistence of pulmonary diseases were more susceptible to lung cancer.,Affected persons deserve greater attention while undergoing cancer screening. | 1 |
Chronic obstructive pulmonary disease (COPD) exacerbations are acute events of worsened respiratory symptoms and enhanced inflammation partly mediated by NF-κB activation.,RelB, an NF-κB family member, suppresses cigarette smoke-induced inflammation but its expression in COPD is unknown.,Moreover, there is no information on its association with clinical features of COPD.,The objectives of this study were to assess RelB expression relative to markers of inflammation as well as its association with cardiovascular and pulmonary features of COPD patients at stable-state and exacerbation.,Data from 48 COPD patients were analyzed.,Blood samples were collected from stable-state and exacerbating patients.,After RNA isolation, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to assess RelB, Cox-2, IL-8 and IL-1β mRNA expression and their associations with measured clinical variables.,Of the 48 COPD subjects, 18 were in stable-state and 30 were in exacerbation.,RelB mRNA expression was lower than that of Cox-2, IL-8, and IL-1β in all cases (all p<0.001, except for IL-8 at exacerbation (p = 0.22)).,Cox-2, IL-8 and IL-1β were significantly associated with clinical features of patients in both stable-state and at exacerbation.,There was no association with RelB expression and any clinical features in COPD subjects at stable-state.,RelB mRNA levels were significantly associated with cardiovascular events such as systolic blood pressure during exacerbation.,RelB mRNA expression is lower than that of the other inflammatory mediators.,Expression of Cox-2, IL-8 and IL-1β were related to clinical features in both stable-state and at exacerbation.,However, RelB expression was associated with clinical features of patients only during exacerbation, suggesting that RelB may represent a novel marker of health outcomes, in particular cardiovascular, during exacerbation in COPD. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
Bronchiectasis revealed by chest computed tomography in COPD patients and its comorbid effect on prognosis have not been addressed by large-sized studies.,Understanding the presence of bronchiectasis in COPD is important for future intervention and preventing disease progression.,Observational studies were identified from electronic literature searches in Cochrane library, PubMed, ScienceDirect databases, American Thoracic Society and European Respiratory Society meeting abstracts.,A systematic review and meta-analysis of studies was performed to summarize the factors associated with bronchiectasis in COPD patients.,Primary outcomes included the risks for exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality.,Odds ratios (ORs) were pooled by random effects models.,Fourteen observational studies were eligible for the study.,Compared with COPD without bronchiectasis, comorbid bronchiectasis in COPD increased the risk of exacerbation (1.97, 95% CI, 1.29-3.00), isolation of a potentially pathogenic microorganism (4.11, 95%CI, 2.16-7.82), severe airway obstruction (1.31, 95% CI, 1.09-1.58) and mortality (1.96, 95% CI, 1.04-3.70).,The presence of bronchiectasis in patients with COPD was associated with exacerbation frequency, isolation of a potentially pathogenic microorganism, severe airway obstruction and mortality. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
To assess the effect of telehealthcare compared with usual practice in patients with chronic obstructive pulmonary disease (COPD).,A cluster-randomised trial with 26 municipal districts that were randomly assigned either to an intervention group whose members received telehealthcare in addition to usual practice or to a control group whose members received usual practice only (13 districts in each arm).,Twenty-six municipal districts in the North Denmark Region of Denmark.,Patients who fulfilled the Global Initiative for COPD guidelines and one of the following criteria: COPD Assessment Test score ≥10; or Medical Research Dyspnoea Council Scale ≥3; or Modified Medical Research Dyspnoea Council Scale ≥2; or ≥2 exacerbations during the past 12 months.,Health-related quality of life (HRQoL) assessed by the physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 36-Item Health Survey, Version 2.,Data were collected at baseline and at 12 month follow-up and analysed according to the intention-to-treat principle with complete cases, n=574 (258 interventions; 316 controls) and imputed data, n=1225 (578 interventions, 647 controls) using multilevel modelling.,In the intention-to-treat analysis (n=1225), the raw mean difference in PCS from baseline to 12 month follow-up was −2.6 (SD 12.4) in the telehealthcare group and −2.8 (SD 11.9) in the usual practice group.,The raw mean difference in MCS scores in the same period was −4.7 (SD 16.5) and −5.3 (SD 15.5) for telehealthcare and usual practice, respectively.,The adjusted mean difference in PCS and MCS between groups at 12 months was 0.1 (95% CI −1.4 to 1.7) and 0.4 (95% CI −1.7 to 2.4), respectively.,The overall sample and all subgroups demonstrated no statistically significant differences in HRQoL between telehealthcare and usual practice.,NCT01984840; Results. | The increasing prevalence and associated cost of treating chronic obstructive pulmonary disease (COPD) is unsustainable, and focus is needed on self-management and prevention of hospital admissions.,Telehealth monitoring of patients’ vital signs allows clinicians to prioritise their workload and enables patients to take more responsibility for their health.,This paper reports the results of a pilot randomised controlled trial (RCT) of Telehealth-supported care within a community-based COPD supported-discharge service.,A two-arm pragmatic pilot RCT was conducted comparing the standard service with a Telehealth-supported service and assessed the potential for progressing into a full RCT.,The co-primary outcome measures were the proportion of COPD patients readmitted to hospital and changes in patients’ self-reported quality of life.,The objectives were to assess the suitability of the methodology, produce a sample size calculation for a full RCT, and to give an indication of cost-effectiveness for both pathways.,Sixty three participants were recruited (n = 31 Standard; n = 32 Telehealth); 15 participants were excluded from analysis due to inadequate data completion or withdrawal from the Telehealth arm.,Recruitment was slow with significant gaps in data collection, due predominantly to an unanticipated 60% reduction of staff capacity within the clinical team.,The sample size calculation was guided by estimates of clinically important effects and COPD readmission rates derived from the literature.,Descriptive analyses showed that the standard service group had a lower proportion of patients with hospital readmissions and a greater increase in self-reported quality of life compared to the Telehealth-supported group.,Telehealth was cost-effective only if hospital admissions data were excluded.,Slow recruitment rates and service reconfigurations prevented progression to a full RCT.,Although there are advantages to conducting an RCT with data collection conducted by a frontline clinical team, in this case, challenges arose when resources within the team were reduced by external events.,Gaps in data collection were resolved by recruiting a research nurse.,This study reinforces previous findings regarding the difficulty of undertaking evaluation of complex interventions, and provides recommendations for the introduction and evaluation of complex interventions within clinical settings, such as prioritisation of research within the clinical remit.,Current Controlled Trials ISRCTN68856013, registered Nov 2010. | 1 |
Comorbidities adversely affect the quality of life and survival of patients with chronic obstructive pulmonary disease (COPD), and timely identification and management of comorbidities are important in caring for COPD patients.,This study aimed to investigate the impact of COPD on long-term developmental trajectories of its comorbidities.,From 2010 to 2013, all spirometry-confirmed COPD patients with a 5-year follow-up period were identified as the cases.,The prevalence of comorbidities and their trajectories in COPD cases were obtained and compared with those in non-COPD controls matched for age, sex, smoking status and Charlson comorbidity index (CCI).,Over the study period, a total of 682 patients, 341 each in COPD and control groups were included, with a mean age of 69.1 years and 89% male.,The baseline mean CCI was 1.9 for both groups of patients and significantly increased to 3.4 and 2.7 in COPD and control groups after 5 years, respectively (both P < 0.001).,Through the 5-year follow-up, a significant increase in the prevalence of all comorbidities of interest was observed in the COPD cohort and the incidence was remarkably higher for hypertension [incidence rate ratio (IRR) 1.495; 95% confidence interval (CI) 1.017-2.198], malignancy (IRR 2.397; 95% CI 1.408-4.081), diabetes mellitus (IRR 2.927; 95% CI 1.612-5.318), heart failure (IRR 2.531; 95% CI 1.502-4.265) and peptic ulcer disease (IRR 2.073; 95% CI 1.176-3.654) as compared to the non-COPD matched controls.,In conclusion, our findings suggest that the presence of COPD may be considered a pathogenic factor involved in the development of certain comorbidities. | COPD has attracted widespread attention worldwide.,The prevalence of COPD in Taiwan has been reported, but little is known about trends in health care resource utilization and pharmacologic management in COPD treatment.,The objective of this article was to study trends in health care resource utilization, pharmacologic management, and medical costs of COPD treatment in Taiwan.,Reimbursement claims in the Taiwan National Health Insurance System from 2004 to 2010 were collected.,The disease burden of COPD, including health care resource utilization and medical costs, was evaluated.,The pharmacy cost of COPD increased from 2004 to 2010 due to the increased utilization of long-acting muscarinic antagonist (LAMA) and fixed-dose combination of long-acting β2-agonist and inhaled corticosteroid (LABA/ICS), whereas the cost of all other COPD-related medications decreased.,The average outpatient department (OPD) cost per patient increased 29.3% from 1,070 USD in 2004 to 1,383 USD in 2010.,The highest average total medical cost per patient was 3,434 USD in 2005, and it decreased 12.4% to 3,008 USD in 2010.,There was no significant difference in the average number of OPD visits and emergency department visits per patient.,The highest average number of hospital admissions was 0.81 in 2005, and it decreased to 0.65 in 2010.,The average number of intensive care unit (ICU) admissions decreased from 0.52 in 2005 to 0.31 in 2010.,From 2004 to 2010, the average total medical cost per patient of COPD was slightly decreased because of the decreased average number of hospital admissions and ICU admissions.,The costs of both LAMA and LABA/ICS increased, while the cost for all other COPD-related medications decreased.,These findings suggest that the increased utilization of LAMA and LABA/ICS may have contributed to the decreased average number of hospital admissions and ICU admissions in COPD patients from 2004 to 2010. | 1 |
Recent literature has suggested that emphysema and chronic bronchitis, traditionally considered to be entities overlapping within chronic obstructive pulmonary disease (COPD), may be distinct disorders.,Few studies have examined the differences in patient characteristics and health outcomes between these conditions.,This study examined whether COPD phenotypes represent distinct patient populations, in a large nationally representative US sample.,Data were obtained from the 2010 US National Health and Wellness Survey (NHWS).,NHWS respondents (n = 75,000) were categorized as a COPD phenotype based on their self-reported diagnosis of COPD only (n = 970), emphysema only (n = 399), or chronic bronchitis only (n = 2071).,Phenotypes were compared on demographics, health characteristics, treatment patterns, health outcomes, work productivity, and resource use.,Variables were compared using Chi-square and analysis of variance tests for categorical and continuous outcomes, respectively.,Health outcomes were also examined using regression modeling, controlling for demographic and health characteristic covariates.,Patients with chronic bronchitis were significantly younger (51.38 years versus 63.24 years for COPD versus 63.30 years for emphysema, P < 0.05) and more likely to be employed (46.98% versus 23.81% for COPD versus 28.33% for emphysema, P < 0.05).,Relative to the other phenotypes, patients with chronic bronchitis were also significantly more likely to be female, nonwhite, and to exercise currently (all P < 0.05), and were significantly less likely to be a current or former smoker (P < 0.05).,Controlling for demographic and health characteristics, patients self-identified as having COPD only reported significantly worse physical quality of life (adjusted mean 36.69) and health utilities (adjusted mean 0.65) and significantly more absenteeism (adjusted mean 7.08%), presenteeism (adjusted mean 30.73%), overall work impairment (adjusted mean 34.06%), and activity impairment (adjusted mean 46.59%) than the other phenotypes (all P < 0.05).,These results suggest considerable heterogeneity among different COPD phenotypes with respect to demographics, health characteristics, disease characteristics, treatment patterns, and health outcomes.,Research aimed at understanding the differences in patient characteristics and disease presentation of these phenotypes could be used to guide treatment recommendations. | Approximately 210 million people are estimated to have chronic obstructive pulmonary disease [COPD] worldwide.,The burden of disease is known to be high, though less is known about those of a younger age.,The aim of this study was to investigate the wider personal, economic and societal burden of COPD on a cross country working-age cohort.,A cross-country [Brazil, China, Germany, Turkey, US, UK] cross-sectional survey methodology was utilised to answer the research questions. 2426 participants aged 45-67 recruited via a number of recruitment methods specific to each country completed the full survey.,Inclusion criteria were a recalled physician diagnosis of COPD, a smoking history of > 10 pack years and the use of COPD medications in the previous 3 months prior to questioning.,The survey included items from the validated Work Productivity and Activity Impairment [WPAI] scale and the EuroQoL 5 Dimension [EQ-5D] scale.,Disease severity was measured using the 5-point MRC [Medical Research Council] dyspnoea scale as a surrogate measure.,64% had either moderate [n = 1012] or severe [n = 521] COPD, although this varied by country. 75% of the cohort reported at least one comorbid condition.,Quality of life declined with severity of illness [mild, mean EQ-5D score = 0.84; moderate 0.58; severe 0.41].,The annual cost of healthcare utilisation [excluding treatment costs and diagnostic tests] per individual was estimated to be $2,364 [£1,500].,For those remaining in active employment [n: 677]: lost time from work cost the individual an average of $880 [£556] per annum and lifetime losses of $7,365 [£4,661] amounting to $596,000 [£377,000] for the cohort. 447 [~40%] of the working population had retired prematurely because of COPD incurring individual estimated lifetime income losses of $316,000 [£200,000] or a combined total of $141 m [£89.6 m].,As the mean age of retirees was 58.3 and average time since retirement was 4 years, this suggests the average age of retirement is around 54.,This would mean a high societal and economic impact in all study countries, particularly where typical state retirement ages are higher, for example in Brazil, Germany and the UK [65] and the US [65,66,67], compared to Turkey [58 for women, 60 for men] and China [60].,Although generalisation across a broader COPD population is limited due to the varied participant recruitment methods, these data nevertheless suggest that COPD has significant personal, economic and societal burden on working age people.,Further efforts to improve COPD diagnosis and management are required. | 1 |
Objective To assess the effect of second generation, home based telehealth on health related quality of life, anxiety, and depressive symptoms over 12 months in patients with long term conditions.,Design A study of patient reported outcomes (the Whole Systems Demonstrator telehealth questionnaire study; baseline n=1573) was nested in a pragmatic, cluster randomised trial of telehealth (the Whole Systems Demonstrator telehealth trial, n=3230).,General practice was the unit of randomisation, and telehealth was compared with usual care.,Data were collected at baseline, four months (short term), and 12 months (long term).,Primary intention to treat analyses tested treatment effectiveness; multilevel models controlled for clustering by general practice and a range of covariates.,Analyses were conducted for 759 participants who completed questionnaire measures at all three time points (complete case cohort) and 1201 who completed the baseline assessment plus at least one other assessment (available case cohort).,Secondary per protocol analyses tested treatment efficacy and included 633 and 1108 participants in the complete case and available case cohorts, respectively.,Setting Provision of primary and secondary care via general practices, specialist nurses, and hospital clinics in three diverse regions of England (Cornwall, Kent, and Newham), with established integrated health and social care systems.,Participants Patients with chronic obstructive pulmonary disease (COPD), diabetes, or heart failure recruited between May 2008 and December 2009.,Main outcome measures Generic, health related quality of life (assessed by physical and mental health component scores of the SF-12, and the EQ-5D), anxiety (assessed by the six item Brief State-Trait Anxiety Inventory), and depressive symptoms (assessed by the 10 item Centre for Epidemiological Studies Depression Scale).,Results In the intention to treat analyses, differences between treatment groups were small and non-significant for all outcomes in the complete case (0.480≤P≤0.904) or available case (0.181≤P≤0.905) cohorts.,The magnitude of differences between trial arms did not reach the trial defined, minimal clinically important difference (0.3 standardised mean difference) for any outcome in either cohort at four or 12 months.,Per protocol analyses replicated the primary analyses; the main effect of trial arm (telehealth v usual care) was non-significant for any outcome (complete case cohort 0.273≤P≤0.761; available case cohort 0.145≤P≤0.696).,Conclusions Second generation, home based telehealth as implemented in the Whole Systems Demonstrator Evaluation was not effective or efficacious compared with usual care only.,Telehealth did not improve quality of life or psychological outcomes for patients with chronic obstructive pulmonary disease, diabetes, or heart failure over 12 months.,The findings suggest that concerns about potentially deleterious effect of telehealth are unfounded for most patients.,Trial Registration ISRCTN43002091. | Objective To determine whether supported self management in chronic obstructive pulmonary disease (COPD) can reduce hospital readmissions in the United Kingdom.,Design Randomised controlled trial.,Setting Community based intervention in the west of Scotland.,Participants Patients admitted to hospital with acute exacerbation of COPD.,Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly, with ongoing support for 12 months.,Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records; health related quality of life measures were secondary outcomes.,Results 464 patients were randomised, stratified by age, sex, per cent predicted forced expiratory volume in 1 second, recent pulmonary rehabilitation attendance, smoking status, deprivation category of area of residence, and previous COPD admissions.,No difference was found in COPD admissions or death (111/232 (48%) v 108/232 (47%); hazard ratio 1.05, 95% confidence interval 0.80 to 1.38).,Return of health related quality of life questionnaires was poor (n=265; 57%), so that no useful conclusions could be made from these data.,Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables.,In an exploratory analysis, 42% (75/150) of patients in the intervention group were classified as successful self managers at study exit, from review of appropriateness of use of self management therapy.,Predictors of successful self management on stepwise regression were younger age (P=0.012) and living with others (P=0.010).,COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers (20/75 (27%) v 51/105 (49%); hazard ratio 0.44, 0.25 to 0.76; P=0.003).,Conclusion Supported self management had no effect on time to first readmission or death with COPD.,Exploratory subgroup analysis identified a minority of participants who learnt to self manage; this group had a significantly reduced risk of COPD readmission, were younger, and were more likely to be living with others.,Trial registration Clinical trials NCT 00706303. | 1 |
Preserved ratio impaired spirometry (PRISm) is an incompletely understood respiratory condition.,We investigated the incidence and significant predictive factors of chronic obstructive pulmonary disease (COPD) in PRISm patients.,From 11,922 subjects registered in the Korea National Health and Nutrition Examination Survey, never or light smokers, young subjects, and those already medically diagnosed with COPD (defined by ICD-10 code and prescribed medication) were excluded.,The 2666 remaining subjects were categorized into PRISm (normal forced expiratory volume in the first second [FEV1]/force vital capacity [FVC] [≥ 0.7] and low FEV1 (< 80%); n = 313); normal (n = 1666); and unrevealed COPD groups (FEV1/FVC ratio < 0.7; n = 687).,These groups were compared using matched Health Insurance Review and Assessment Service data over a 3-year follow-up.,COPD incidence in PRISm patients (17/1000 person-year [PY]) was higher than that in normal subjects (4.3/1000 PY; P < 0.001), but lower than that in unrevealed COPD patients (45/1000 PY; P < 0.001).,PRISm patients visited hospitals, took COPD medication, and incurred hospitalization costs more frequently than normal subjects, but less frequently than unrevealed COPD patients.,In the overall sample, age, FVC, FEV1, dyspnea, and wheezing were significant predictors of COPD, but in PRISm patients, only age (OR, 1.14; P = 0.002) and wheezing (OR, 4.56; P = 0.04) were significant predictors.,PRISm patients are likely to develop COPD, and should be monitored carefully, especially older patients and those with wheezing, regardless of lung function. | Reasons for the excess risk for cardiovascular disease among people with chronic obstructive pulmonary disease remain unclear.,Our objective was to examine the cardiovascular risk profile for adults with obstructive and restrictive impairments of lung functioning in a representative sample of adults from the United States.,We used data from adults aged 20-79 years who participated in the National Health and Nutrition Examination Survey from 2007 to 2010 and had a pulmonary function test.,The severity of obstructive impairment was defined by adapting the Global Initiative for Chronic Obstructive Lung Disease criteria.,Among 7249 participants, 80.9% had a normal pulmonary function test, 5.7% had a restrictive impairment, 7.9% had mild obstructive impairment, and 5.5% had moderate or severe/very severe obstructive impairment.,Participants with obstructive impairment had high rates of smoking and increased serum concentrations of cotinine.,Compared to participants with normal pulmonary functioning, participants with at least moderate obstructive impairment had elevated concentrations of C-reactive protein but lower concentrations of total cholesterol and non-high-density lipoprotein cholesterol.,Among participants aged 50-74 years, participants with at least a moderate obstructive impairment or a restrictive impairment had an elevated predicted 10-year risk for cardiovascular disease.,The high rates of smoking among adults with impaired pulmonary functioning, particularly those with obstructive impairment, point to a need for aggressive efforts to promote smoking cessation in these adults.,In addition, adults with restrictive impairment may require increased attention to and fine-tuning of their cardiovascular risk profile. | 1 |
Uptake of nutritional supplementation during pulmonary rehabilitation (PR) for people with chronic obstructive pulmonary disease (COPD) has been limited by an absence of rigorous evidence-based studies supporting use.,The objective was to report and summarise the current evidence supporting the use of nutritional supplementation to improve outcomes during PR in stable COPD patients.,A systematic search was conducted up to 7 August 2019 (registration number CRD42018089142).,The preferred reporting items for systematic reviews and meta-analyses guidelines were used.,Six databases were included: Medical Literature Analysis and Retrieval System Online or MEDLARS Online, Allied and Complementary Medicine Database, the Cochrane Database of Systematic Reviews, Excerpta Medica dataBASE, Cumulative Index of Nursing and Allied Health Literature and Web of Science.,This systematic search generated 580 initial matches, of which 22 studies (917 COPD participants) met the pre-specified criteria and were included.,Sixteen of 19 studies that used nutritional supplements in addition to PR did not show additional benefit compared to PR alone when measuring exercise capacity.,Nutritional supplements significantly increased body weight in 7 of 11 studies.,Body mass index increased significantly in two of six studies.,Handgrip strength did not improve, while quadriceps muscle strength significantly improved in 3 of 11 studies.,Four of eight studies showed a significant improvement in inspiratory muscle function.,Only 2 of 14 studies demonstrated a significant improvement in quality of life with supplementation in addition to PR.,There remains insufficient evidence on the effect of nutritional supplementation on improving outcomes during PR in patients with COPD due to heterogeneity in supplements, outcome measures and PR programmes.,Therefore, controversy remains and further research is needed. | Chronic obstructive pulmonary disease (COPD) patients often experience lower limb muscle dysfunction and wasting.,Exercise-based training has potential to improve muscle function and mass, but literature on this topic is extensive and heterogeneous including numerous interventions and outcome measures.,This review uses a detailed systematic approach to investigate the effect of this wide range of exercise-based interventions on muscle function and mass.,PUBMED and PEDro databases were searched.,In all, 70 studies (n = 2504 COPD patients) that implemented an exercise-based intervention and reported muscle strength, endurance, or mass in clinically stable COPD patients were critically appraised.,Aerobic and/or resistance training, high-intensity interval training, electrical or magnetic muscle stimulation, whole-body vibration, and water-based training were investigated.,Muscle strength increased in 78%, muscle endurance in 92%, and muscle mass in 88% of the cases where that specific outcome was measured.,Despite large heterogeneity in exercise-based interventions and outcome measures used, most exercise-based trials showed improvements in muscle strength, endurance, and mass in COPD patients.,Which intervention(s) is (are) best for which subgroup of patients remains currently unknown.,Furthermore, this literature review identifies gaps in the current knowledge and generates recommendations for future research to enhance our knowledge on exercise-based interventions in COPD patients. | 1 |
Endothelial progenitor cells (EPCs) are decreased in cardiac dysfunction morbidity associated with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).,Therefore, the present study aimed to assess the role of EPCs in AECOPD.,Patients with AECOPD (n=27) or stable COPD (n=26) were enrolled.,Systemic inflammatory markers (high-sensitivity C-reactive protein) were measured.,In addition, EPCs were counted, isolated and cultured, and their proliferative, migratory, adhesive and tube-forming capabilities were determined, in cells from patients with AECOPD and stable COPD.,EPC number was lower in patients with AECOPD (5.1±2.6×103/ml) compared with patients with stable COPD (6.0±3.2×103/ml).,Migration assay indicated that the early-EPCs isolated from patients with AECOPD were significantly less mobile than EPCs derived from stable COPD subjects, at a stromal-cell derived factor-1α concentration of 100 ng/ml (3,550/30,000 vs.,7,853/30,000, P<0.05).,C-X-C chemokine receptor-4 positivity was significantly reduced in AECOPD patients (16.1±9.9 vs.,56.33±6.3%, P<0.05).,Furthermore, fewer early-EPC clusters were formed by EPCs derived from AECOPD, compared with those derived from stable COPD (8.2±0.86 vs.,14.4±1.36, P=0.027).,Stable COPD late-EPCs were markedly deficient in intact tubule formation, however AECOPD late-EPCs formed no tubules.,The number of AECOPD- and stable COPD-derived late-EPCs adhering to Matrigel-induced tubules was 36.8±1.85 and 20.6±1.36 (P<0.05) respectively, and the cluster of differentiation 31 positivity in late-EPCs was 79.69±1.3 and 29.1±2.47%, in AECOPD and stable COPD patients, respectively (P<0.001).,The findings demonstrated that early-EPCs are decreased and dysfunctional in AECOPD patients, which may contribute to the altered vascular endothelium in this patient population. | The burden of chronic obstructive pulmonary disease (COPD) across many world regions is high.,We aim to estimate COPD prevalence and number of disease cases for the years 1990 and 2010 across world regions based on the best available evidence in publicly accessible scientific databases.,We conducted a systematic search of Medline, EMBASE and Global Health for original, population-based studies providing spirometry-based prevalence rates of COPD across the world from January 1990 to December 2014.,Random effects meta-analysis was conducted on extracted crude prevalence rates of COPD, with overall summaries of the meta-estimates (and confidence intervals) reported separately for World Health Organization (WHO) regions, the World Bank's income categories and settings (urban and rural).,We developed a meta-regression epidemiological model that we used to estimate the prevalence of COPD in people aged 30 years or more.,Our search returned 37 472 publications.,A total of 123 studies based on a spirometry-defined prevalence were retained for the review.,From the meta-regression epidemiological model, we estimated about 227.3 million COPD cases in the year 1990 among people aged 30 years or more, corresponding to a global prevalence of 10.7% (95% confidence interval (CI) 7.3%-14.0%) in this age group.,The number of COPD cases increased to 384 million in 2010, with a global prevalence of 11.7% (8.4%-15.0%).,This increase of 68.9% was mainly driven by global demographic changes.,Across WHO regions, the highest prevalence was estimated in the Americas (13.3% in 1990 and 15.2% in 2010), and the lowest in South East Asia (7.9% in 1990 and 9.7% in 2010).,The percentage increase in COPD cases between 1990 and 2010 was the highest in the Eastern Mediterranean region (118.7%), followed by the African region (102.1%), while the European region recorded the lowest increase (22.5%).,In 1990, we estimated about 120.9 million COPD cases among urban dwellers (prevalence of 13.2%) and 106.3 million cases among rural dwellers (prevalence of 8.8%).,In 2010, there were more than 230 million COPD cases among urban dwellers (prevalence of 13.6%) and 153.7 million among rural dwellers (prevalence of 9.7%).,The overall prevalence in men aged 30 years or more was 14.3% (95% CI 13.3%-15.3%) compared to 7.6% (95% CI 7.0%-8.2%) in women.,Our findings suggest a high and growing prevalence of COPD, both globally and regionally.,There is a paucity of studies in Africa, South East Asia and the Eastern Mediterranean region.,There is a need for governments, policy makers and international organizations to consider strengthening collaborations to address COPD globally. | 1 |
Patients with COPD who remain symptomatic on long-acting bronchodilator monotherapy may benefit from step-up therapy to a long-acting bronchodilator combination.,This study evaluated the efficacy and safety of umeclidinium (UMEC)/vilanterol (VI) in patients with moderate COPD who remained symptomatic on tiotropium (TIO).,In this randomized, blinded, double-dummy, parallel-group study (NCT01899742), patients (N=494) who were prescribed TIO for ≥3 months at screening (forced expiratory volume in 1 s [FEV1]: 50%-70% of predicted; modified Medical Research Council [mMRC] score ≥1) and completed a 4-week run-in with TIO were randomized to UMEC/VI 62.5/25 µg or TIO 18 µg for 12 weeks.,Efficacy assessments included trough FEV1 at Day 85 (primary end point), 0-3 h serial FEV1, rescue medication use, Transition Dyspnea Index (TDI), St George’s Respiratory Questionnaire (SGRQ), and COPD Assessment Test (CAT).,Safety evaluations included adverse events (AEs).,Compared with TIO, UMEC/VI produced greater improvements in trough FEV1 (least squares [LS] mean difference: 88 mL at Day 85 [95% confidence interval {CI}: 45-131]; P<0.001) and FEV1 after 5 min on Day 1 (50 mL [95% CI: 27-72]; P<0.001).,Reductions in rescue medication use over 12 weeks were greater with UMEC/VI versus TIO (LS mean change: −0.1 puffs/d [95% CI: −0.2-0.0]; P≤0.05).,More patients achieved clinically meaningful improvements in TDI score (≥1 unit) with UMEC/VI (63%) versus TIO (49%; odds ratio at Day 84=1.78 [95% CI: 1.21-2.64]; P≤0.01).,Improvements in SGRQ and CAT scores were similar between treatments.,The incidence of AEs was similar with UMEC/VI (30%) and TIO (31%).,UMEC/VI step-up therapy provides clinical benefit over TIO monotherapy in patients with moderate COPD who are symptomatic on TIO alone. | The benefits of pharmacotherapy with tiotropium HandiHaler 18 μg for patients with chronic obstructive pulmonary disease (COPD) have been previously demonstrated.,However, few data exist regarding the treatment of moderate disease (Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II).,To determine whether tiotropium improves lung function/patient-reported outcomes in patients with GOLD stage II COPD naive to maintenance therapy.,A randomised 24-week double-blind placebo-controlled trial of tiotropium 18 μg once daily (via HandiHaler) was performed in maintenance therapy-naive patients with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio <0.7 and post-bronchodilator FEV1 ⩾50 and <80%.,A total of 457 patients were randomised (238 tiotropium, 219 placebo; mean age 62 years; FEV1 1.93 l (66% predicted)).,Tiotropium was superior to placebo in mean change from baseline in post-dose FEV1 area under the curve from 0 to 3 h (AUC0-3h) at week 24 (primary endpoint): 0.19 vs.,−0.03 l (least-squares mean difference 0.23 l, P<0.001).,FVC AUC0-3h, trough and peak FEV1 and FVC were significantly improved with tiotropium versus placebo (P<0.001).,Compared with placebo, tiotropium provided numerical improvements in physical activity (P=NS).,Physician’s Global Assessment (health status) improved (P=0.045) with less impairment on the Work Productivity and Activity Impairment questionnaire (P=0.043) at week 24.,The incidence of exacerbations, cough, bronchitis and dyspnoea was lower with tiotropium than placebo.,Tiotropium improved lung function and patient-reported outcomes in maintenance therapy-naive patients with GOLD stage II COPD, suggesting benefits in initiating maintenance therapy early. | 1 |
Currently, chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide.,The determination of immune mechanisms of inflammation in the disease presents an important challenge for fundamental medical research.,According to modern views, Toll-like receptors (TLRs), among which TLR2 and TLR4 play a key role, are one of the essential components of inflammatory process in COPD.,This review focuses on following aspects: the role of TLR2 and TLR4 in the initiation of inflammatory process in COPD; the mechanisms of influence of various exogenous factors (cigarette smoke, suspended particulate matter, and bacteria) on the expression of TLR2 and TLR4; the contribution of these TLRs to the T-helper (Th) immune response development in COPD, in particular to the Th17 immune response, which contributes to the progression of the disease and therapeutic implications of TLR2 and TLR4 in COPD. | Cachexia is associated with increased mortality risk among chronic obstructive pulmonary disease (COPD) patients.,However, low body mass index (BMI) as opposed to cachexia is often used, particularly when calculating the BODE (BMI, Obstruction, Dyspnea and Exercise) index.,For this reason, we examined mortality using a consensus definition and a weight-loss definition of cachexia among COPD cases and compared two new COPD severity indices with BODE.,In the current report, the consensus definition for cachexia incorporated weight-loss > 5% in 12-months or low BMI in addition to 3/5 of decreased muscle strength, fatigue, anorexia, low FFMI and inflammation.,The weight-loss definition incorporated weight-loss > 5% or weight-loss > 2% (if low BMI) in 12-months.,The low BMI component in BODE was replaced with the consensus definition to create the CODE (Consensus cachexia, Obstruction, Dyspnea and Exercise) index and the weight-loss definition to create the WODE (Weight loss, Obstruction, Dyspnea and Exercise) index.,Mortality was assessed using Kaplan-Meier survival and Cox Regression.,Performance of models was compared using C-statistics.,Among 1483 COPD cases, the prevalences of cachexia by the consensus and weight-loss definitions were 4.7 and 10.4%, respectively.,Cachectic patients had a greater than three-fold increased mortality by either the consensus or the weight-loss definition of cachexia independent of BMI and lung function.,The CODE index predicted mortality slightly more accurately than the BODE and WODE indices.,Cachexia is associated with increased mortality among COPD patients.,Monitoring cachexia using weight-loss criteria is relatively simple and predictive of mortality among COPD cases who may be missed if only low BMI is used.,The online version of this article (10.1186/s12931-019-1073-3) contains supplementary material, which is available to authorized users. | 1 |
Indacaterol is a novel, once-daily (od), inhaled, long-acting ß2-agonist bronchodilator for maintenance treatment of airflow limitation in patients with COPD.,The aim of this study was to evaluate the efficacy of indacaterol on dyspnea, using available randomized placebo-controlled trials.,A systematic search was made of MEDLINE, EMBASE, the Cochrane trials databases, and a manual search of journals.,Randomized placebo-controlled trials of 12 weeks or more comparing indacaterol with placebo were reviewed, and eligible studies were included in a meta-analysis.,The odds ratio (OR) for likelihood of achieving TDI score ≥ 1 after 12 weeks of treatment was used as an outcome measure to compare indacaterol to placebo.,Six trials were included in the analysis.,Relative to placebo, the overall ORs for response were: indacaterol 75 μg od 1.784 (95% CI 1.282 to 2.482); indacaterol 150 μg od 2.149 (95% CI 1.746 to 2.645); and indacaterol 300 μg od 2.458 (95% CI 2.010 to 3.006).,Overall OR for response in TDI tended to increase with higher indacaterol doses.,Patients receiving indacaterol had clinically significant improvements in symptoms of dyspnea compared to placebo.,Incremental benefits in TDI were observed with increasing doses.,Indacaterol may provide patients and physicians with a useful treatment option in symptomatic patients with dyspnea. | Although medical treatment of COPD has advanced, nonadherence to medication regimens poses a significant barrier to optimal management.,Underuse, overuse, and improper use continue to be the most common causes of poor adherence to therapy.,An average of 40%-60% of patients with COPD adheres to the prescribed regimen and only 1 out of 10 patients with a metered dose inhaler performs all essential steps correctly.,Adherence to therapy is multifactorial and involves both the patient and the primary care provider.,The effect of patient instruction on inhaler adherence and rescue medication utilization in patients with COPD does not seem to parallel the good results reported in patients with asthma.,While use of a combined inhaler may facilitate adherence to medications and improve efficacy, pharmacoeconomic factors may influence patient’s selection of both the device and the regimen.,Patient’s health beliefs, experiences, and behaviors play a significant role in adherence to pharmacological therapy.,This manuscript reviews important aspects associated with medication adherence in patients with COPD and identifies some predictors of poor adherence. | 1 |
The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known.,We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database.,951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012.,Individuals were selected for ≥1 of 8 algorithms to identify people with COPD.,General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested.,All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard.,The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed.,951 questionnaires were sent and 738 (78%) returned.,After quality control, 696 (73.2%) patients were included in the final analysis.,All four algorithms including a specific COPD diagnostic code performed well.,Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%.,Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%).,Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes.,Requiring spirometry or COPD medications only marginally improved accuracy.,The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. | Chronic obstructive pulmonary disease (COPD) is a major public health problem, associated with considerable morbidity and health care costs.,The global burden of COPD morbidity is predicted to rise substantially in the coming decade, but could be moderated by better use of existing management strategies.,Smoking cessation, medication therapy, and pulmonary rehabilitation have all been shown to diminish morbidity and improve patient outcomes.,But each of these strategies requires adherence.,Adherence is crucial for optimizing clinical outcomes in COPD, with nonadherence resulting in a significant health and economic burden.,Suboptimal medication adherence is common among COPD patients, due to a number of factors that involve the medication, the delivery device, the patient, and the health professionals caring for the patient.,Lack of medication adherence needs to be identified and addressed by using simplified treatment regimens, increasing patient knowledge about self-management, and enhancing provider skills in patient education, communication, and adherence counseling.,This article reports some of the challenges of medication nonadherence faced by the clinician in the management of COPD, and suggests ways to evaluate and improve adherence effectively in primary care. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by chronic pulmonary and systematic inflammation.,An abnormal adaptive immune response leads to an imbalance between pro- and anti-inflammatory processes.,T-helper (Th), T-cytotoxic (Tc) and T-regulatory (Treg) cells may play important roles in immune and inflammatory responses.,This study was conducted to clarify the changes and imbalance of cytokines and T lymphocyte subsets in patients with COPD, especially during acute exacerbations (AECOPD).,Twenty-three patients with stable COPD (SCOPD) and 21 patients with AECOPD were enrolled in the present study.,In addition, 20 age-, sex- and weight-matched non-smoking healthy volunteers were included as controls.,The serum levels of selected cytokines (TGF-β, IL-10, TNF-α, IL-17 and IL-9) were measured by enzyme-linked immunosorbent assay (ELISA) kits.,Furthermore, the T lymphocyte subsets collected from peripheral blood samples were evaluated by flow cytometry after staining with anti-CD3-APC, anti-CD4-PerCP, anti-CD8- PerCP, anti-CD25-FITC and anti-FoxP3-PE monoclonal antibodies.,Importantly, to remove the confounding effects of inflammatory factors, the authors introduced a concept of “inflammation adjustment” and corrected each measured value using representative inflammatory markers, such as TNF-α and IL-17.,Unlike the other cytokines, serum TGF-β levels were considerably higher in patients with AECOPD relative to the control group regardless of adjustment.,There were no significant differences in the percentages of either CD4+ or CD8+ T cells among the three groups.,Although Tregs were relatively upregulated during acute exacerbations, their capacities of generation and differentiation were far from sufficient.,Finally, the authors noted that the ratios of Treg/IL-17 were similar among groups.,These observations suggest that in patients with COPD, especially during acute exacerbations, both pro-inflammatory and anti-inflammatory reactions are strengthened, with the pro-inflammatory reactions dominating.,Although the Treg/IL-17 ratios were normal, the regulatory T cells were still insufficient to suppress the accompanying increases in inflammation.,All of these changes suggest a complicated mechanism of pro- and anti-inflammatory imbalance which needs to be further investigated. | Lung CD4+ T cells accumulate as chronic obstructive pulmonary disease (COPD) progresses, but their role in pathogenesis remains controversial.,To address this controversy, we studied lung tissue from 53 subjects undergoing clinically-indicated resections, lung volume reduction, or transplant.,Viable single-cell suspensions were analyzed by flow cytometry or underwent CD4+ T cell isolation, followed either by stimulation with anti-CD3 and cytokine/chemokine measurement, or by real-time PCR analysis.,In lung CD4+ T cells of most COPD subjects, relative to lung CD4+ T cells in smokers with normal spirometry: (a) stimulation induced minimal IFN-γ or other inflammatory mediators, but many subjects produced more CCL2; (b) the T effector memory subset was less uniformly predominant, without correlation with decreased IFN-γ production.,Analysis of unstimulated lung CD4+ T cells of all subjects identified a molecular phenotype, mainly in COPD, characterized by markedly reduced mRNA transcripts for the transcription factors controlling TH1, TH2, TH17 and FOXP3+ T regulatory subsets and their signature cytokines.,This mRNA-defined CD4+ T cell phenotype did not result from global inability to elaborate mRNA; increased transcripts for inhibitory CD28 family members or markers of anergy; or reduced telomerase length.,As a group, these subjects had significantly worse spirometry, but not DLCO, relative to subjects whose lung CD4+ T cells expressed a variety of transcripts.,Analysis of mRNA transcripts of unstimulated lung CD4+ T cell among all subjects identified two distinct molecular correlates of classical COPD clinical phenotypes: basal IL-10 transcripts correlated independently and inversely with emphysema extent (but not spirometry); by contrast, unstimulated IFN-γ transcripts correlated independently and inversely with reduced spirometry (but not reduced DLCO or emphysema extent).,Aberrant lung CD4+ T cells polarization appears to be common in advanced COPD, but also exists in some smokers with normal spirometry, and may contribute to development and progression of specific COPD phenotypes.,ClinicalTrials.gov as NCT00281229 | 1 |
Patients with COPD experience lower airway and systemic inflammation, and an accelerated decline in FEV1.,There is no evidence on whether this inflammation changes over time, or if it is associated with a faster decline in FEV1.,A cohort of 148 COPD patients (100 men) was monitored daily for a median of 2.91 years (interquartile range [IQR], 2.1 to 4.8).,At recruitment, median age was 68.5 years (IQR, 62.5 to 73.6) and FEV1 as percentage of predicted (FEV1%Pred) was 38.5% (IQR, 27.7 to 50.3).,During the study, the patients experienced 1,389 exacerbations, a median of 2.52/yr (IQR, 1.48 to 3.96) and FEV1 declined by 40.2 mL/yr or as FEV1%Pred by 1.5%/yr.,Concerning inflammatory markers, sputum interleukin (IL)-6 rose by 9 pg/mL/yr, sputum neutrophil count rose by 1.64 × 106 cells per gram sputum per year, an plasma fibrinogen rose by 0.10 g/L/yr (all p < 0.05).,Patients with frequent exacerbations (≥ 2.52/yr) had a faster rise over time in plasma fibrinogen and sputum IL-6 of 0.063 g/L/yr (p = 0.046, n = 130) and 29.5 pg/mL/yr (p < 0.001, n = 98), respectively, compared to patients with infrequent exacerbations (< 2.52/yr).,Using the earliest stable (nonexacerbation) measured marker, patients whose IL-6 exceeded the group median had a faster FEV1%Pred decline of 0.42%/yr (p = 0.018).,Similarly, a high neutrophil count or fibrinogen were associated with a faster FEV1%Pred decline of 0.97%/yr (p = 0.001) and 0.40%/yr (p = 0.014), respectively.,In COPD, airway and systemic inflammatory markers increase over time; high levels of these markers are associated with a faster decline in lung function. | The relationship between physical activity, disease severity, health status and prognosis in patients with COPD has not been systematically assessed.,Our aim was to identify and summarise studies assessing associations between physical activity and its determinants and/or outcomes in patients with COPD and to develop a conceptual model for physical activity in COPD.,We conducted a systematic search of four databases (Medline, Embase, CINAHL and Psychinfo) prior to November 2012.,Teams of two reviewers independently selected articles, extracted data and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) to assess quality of evidence.,86 studies were included: 59 were focused on determinants, 23 on outcomes and 4 on both.,Hyperinflation, exercise capacity, dyspnoea, previous exacerbations, gas exchange, systemic inflammation, quality of life and self-efficacy were consistently related to physical activity, but often based on cross-sectional studies and low-quality evidence.,Results from studies of pharmacological and non-pharmacological treatments were inconsistent and the quality of evidence was low to very low.,As outcomes, COPD exacerbations and mortality were consistently associated with low levels of physical activity based on moderate quality evidence.,Physical activity was associated with other outcomes such as dyspnoea, health-related quality of life, exercise capacity and FEV1 but based on cross-sectional studies and low to very low quality evidence.,Physical activity level in COPD is consistently associated with mortality and exacerbations, but there is poor evidence about determinants of physical activity, including the impact of treatment. | 1 |
The efficacy and safety of once-daily tiotropium + olodaterol (T+O) maintenance treatment was demonstrated in the large, multinational, replicate, randomized, Phase III, Tonado® 1 (NCT01431274) and 2 (NCT01431287) studies in patients with moderate to very severe COPD.,However, there may be racial differences in the effects of T+O on lung function in patients with COPD.,In this Tonado® subgroup analysis, we assessed efficacy and safety of T+O in Japanese participants.,Versus the overall population, the 413 Japanese patients randomized and treated were slightly older, with more men, lower body mass index, lower baseline St George’s Respiratory Questionnaire (SGRQ) scores, fewer current smokers, but with higher pack-year smoking history.,A lower proportion of Japanese patients used inhaled corticosteroids, short-acting muscarinic antagonists, or short- or long-acting β-adrenergic agonists at baseline, but use of long-acting muscarinic antagonists was higher.,At Week 24, mean improvements with T+O 5/5 μg in forced expiratory volume in 1 second area under the curve from 0-3 hours response were 151 mL versus olodaterol and 134 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 87 mL versus olodaterol and 70 mL versus tiotropium 2.5 μg.,Mean improvements with T+O 5/5 μg in trough forced expiratory volume in 1 second were 131 mL versus olodaterol and 108 mL versus tiotropium 5 μg; mean improvements with T+O 2.5/5 μg were 60 mL versus olodaterol and 47 mL versus tiotropium 2.5 μg.,SGRQ scores improved from baseline to a greater extent with both doses of T+O versus monotherapies.,Responses were similar in the overall population.,Adverse-event incidence was generally balanced across treatment groups.,Consistent with results from the overall population, T+O 5/5 μg was superior to each monotherapy for lung function and SGRQ in the Japanese sub-population of patients with COPD in Tonado®. | Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | 1 |
Cardiovascular diseases (CVDs) are arguably the most important comorbidities in chronic obstructive pulmonary disease (COPD).,CVDs are common in people with COPD, and their presence is associated with increased risk for hospitalization, longer length of stay and all-cause and CVD-related mortality.,The economic burden associated with CVD in this population is considerable and the cumulative cost of treating comorbidities may even exceed that of treating COPD itself.,Our understanding of the biological mechanisms that link COPD and various forms of CVD has improved significantly over the past decade.,But despite broad acceptance of the prognostic significance of CVDs in COPD, there remains widespread under-recognition and undertreatment of comorbid CVD in this population.,The reasons for this are unclear; however institutional barriers and a lack of evidence-based guidelines for the management of CVD in people with COPD may be contributory factors.,In this review, we summarize current knowledge relating to the prevalence and incidence of CVD in people with COPD and the mechanisms that underlie their coexistence.,We discuss the implications for clinical practice and highlight opportunities for improved prevention and treatment of CVD in people with COPD.,While we advocate more active assessment for signs of cardiovascular conditions across all age groups and all stages of COPD severity, we suggest targeting those aged under 65 years.,Evidence indicates that the increased risks for CVD are particularly pronounced in COPD patients in mid-to-late-middle-age and thus it is in this age group that the benefits of early intervention may prove to be the most effective. | The European Community Respiratory Health Survey is a major international study designed to assess lung health in adults.,This Australian follow-up investigated changes in symptoms between sexes and the roles of asthma, smoking, age, sex, height, and change in body mass index (ΔBMI) on lung function decline (LFD), which is a major risk factor for chronic obstructive pulmonary disease (COPD).,LFD was measured as the rate of decline over time in FEV1 (mL/year) (ΔFEV1) and FVC (ΔFVC) between 1993 and 2013.,Multiple linear regression was used to estimate associations between risk factors and LFD, separately for males and females.,Multiple logistic regression was used to assess sex differences and changes in respiratory symptoms over time.,In Melbourne, 318 subjects (53.8% females) participated.,The prevalence of most respiratory symptoms had either remained relatively stable over 20 years or decreased (significantly so for wheeze).,The exception was shortness of breath after activity, which had increased.,Among the 262 subjects who completed spirometry, current smoking declined from 20.2% to 7.3%.,Overall mean (± standard deviation) FEV1 declined by 23.1 (±17.1) and FVC by 22.9 (±20.2) mL/year.,Predictors of ΔFEV1 in males were age, maternal smoking, and baseline FEV1; and in females they were age, ΔBMI, baseline FEV1, and pack-years in current smokers.,Decline in FVC was predicted by baseline FVC, age, and ΔBMI in both sexes; however, baseline FVC predicted steeper decline in females than males.,Most respiratory symptoms remained stable or decreased over time in both sexes.,Age, baseline lung function, and change in BMI were associated with the rate of decline in both sexes.,However, obesity and personal smoking appear to put females at higher risk of LFD than males.,Health promotion campaigns should particularly target females to prevent COPD. | 1 |
The Short Physical Performance Battery (SPPB) is an assessment tool with good prognostic value in COPD.,It includes the following: standing balance, 4 m gait speed test (4MGS), and the timed five-repetition sit-to-stand test (5STS).,The specific differences in determinants between these three tasks have not been adequately characterized in COPD patients.,We aimed to identify health-related, functional, and psychological determinants of each SPPB test.,We conducted a cross-sectional analysis of 137 patients with stable COPD.,Patients performed the SPPB, quadriceps muscle strength (QMS), exercise tolerance test (6-min walk test [6MWT]), and pulmonary function; and health-related and psychological factors, physical activity, the COPD assessment test (CAT), body mass index, age, and depression were assessed.,Separate multivariable regression models predicting the 4MGS, 5STS, and balance test results described 31%, 39.1%, and 12.1% of the variance for each test, respectively.,QMS was negatively associated with all three tests.,The 6MWT was negatively associated with the 4MGS and 5STS.,Depression and age were positively associated with 4MGS scores, whereas CAT and age were positively associated with 5STS scores.,The three SPPB tests did not provide equivalent information regarding a COPD patient’s status.,The 5STS was associated with health status factors, while the 4MGS was associated with psychological factors. | Chronic obstructive pulmonary disease (COPD) is a respiratory disease that results in airflow limitation and respiratory distress, also having many nonrespiratory manifestations that affect both function and mobility.,Preliminary evidence suggests that balance deficits constitute an important secondary impairment in individuals with COPD.,Our objective was to investigate balance performance in two groups of COPD patients with different body compositions and to observe which of these groups are more likely to experience falls in the future.,We included 27 stable COPD patients and 17 healthy individuals who performed a series of balance tests.,The COPD patients were divided in two groups: emphysematous and bronchitic.,Patients completed the activities balance confidence scale and the COPD assessment test questionnaire and afterward performed the Berg Balance Scale, timed up and go, single leg stance and 6-minute walking distance test.,We analyzed the differences in the balance tests between the studied groups.,Bronchitic COPD was associated with a decreased value when compared to emphysematous COPD for the following variables: single leg stance (8.7 vs 15.6; P<0.001) and activities balance confidence (53.2 vs 74.2; P=0.001).,Bronchitic COPD patients had a significantly higher value of timed up and go test compared to patients with emphysematous COPD (14.7 vs 12.8; P=0.001).,Patients with COPD have a higher balance impairment than their healthy peers.,Moreover, we observed that the bronchitic COPD phenotype is more likely to experience falls compared to the emphysematous phenotype. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | Measuring dyspnea intensity associated with exercise provides insights into dyspnea-limited exercise capacity, and has been used to evaluate treatment outcomes for chronic obstructive pulmonary disease (COPD).,Three patient-reported outcome scales commonly cited for rating dyspnea during exercise are the modified Borg scale (MBS), numerical rating scale for dyspnea (NRS-D), and visual analogue scale for dyspnea (VAS-D).,Various versions of each scale were found.,Our objective was to evaluate the content validity of scales commonly used in COPD studies, to explore their ability to capture patients’ experiences of dyspnea during exercise, and to evaluate a standardized version of the MBS.,A two-stage procedure was used, with each stage involving one-on-one interviews with COPD patients who had recently completed a clinic-based exercise event on a treadmill or cycle ergometer.,An open-ended elicitation interview technique was used to understand patients’ experiences of exercise-induced dyspnea, followed by patients completing the three scales.,The cognitive interviewing component of the study involved specific questions to evaluate the patients’ perspectives of the content and format of the scales.,Results from Stage 1 were used to develop a standardized version of the MBS, which was then subjected to further content validity assessment during Stage 2.,Thirteen patients participated in the two-stage process (n = 6; n = 7).,Mean forced expiratory volume in 1 second (FEV1) percent predicted was 40%, mean age 57 years, and 54% were male.,Participants used a variety of terms to describe the intensity and variability of exercise-induced dyspnea.,Subjects understood the instructions and format of the standardized MBS, and were able to easily select a response to report the level of dyspnea associated with their recent standardized exercise.,This study provides initial evidence in support of using a standardized version of the MBS version for quantifying dyspnea intensity associated with exercise in patients with COPD. | 1 |
Given the heterogeneity of chronic obstructive pulmonary disease (COPD), personalized clinical management is key to optimizing patient outcomes.,Important treatment goals include minimizing disease activity and preventing disease progression; however, quantification of these components remains a challenge.,Growing evidence suggests that decline over time in forced expiratory volume in 1 s (FEV1), traditionally the key marker of disease progression, may not be sufficient to fully determine deterioration across COPD populations.,In addition, there is a lack of evidence showing that currently available multidimensional COPD indexes improve clinical decision-making, treatment, or patient outcomes.,The composite clinically important deterioration (CID) endpoint was developed to assess disease worsening by detecting early deteriorations in lung function (measured by FEV1), health status (assessed by the St George’s Respiratory Questionnaire), and the presence of exacerbations.,Post hoc and prospective analyses of clinical trial data have confirmed that the multidimensional composite CID endpoint better predicts poorer medium-term outcomes compared with any single CID component alone, and that it can demonstrate differences in treatment efficacy in short-term trials.,Given the widely acknowledged need for an individualized holistic approach to COPD management, monitoring short-term CID has the potential to facilitate early identification of suboptimal treatment responses and patients at risk of increased disease progression.,CID monitoring may lead to better-informed clinical management decisions and potentially improved prognosis. | Combining two long-acting bronchodilators with complementary mechanisms of action may provide treatment benefits to patients with chronic obstructive pulmonary disease (COPD) that are greater than those derived from either treatment alone.,The efficacy and safety of a fixed-dose combination (FDC) of aclidinium bromide, a long-acting muscarinic antagonist, and formoterol fumarate, a long-acting β2-agonist, in patients with moderate to severe COPD are presented.,In this 24-week double-blind study, 1692 patients with stable COPD were equally randomized to twice-daily treatment with FDC aclidinium 400 μg/formoterol 12 μg (ACL400/FOR12 FDC), FDC aclidinium 400 μg/formoterol 6 μg (ACL400/FOR6 FDC), aclidinium 400 μg, formoterol 12 μg, or placebo administered by a multidose dry powder inhaler (Genuair®/Pressair®)*.,Coprimary endpoints were change from baseline to week 24 in 1-hour morning postdose FEV1 (FDCs versus aclidinium) and change from baseline to week 24 in morning predose (trough) FEV1 (FDCs versus formoterol).,Secondary endpoints were change from baseline in St.,George’s Respiratory Questionnaire (SGRQ) total score and improvement in Transition Dyspnea Index (TDI) focal score at week 24.,Safety and tolerability were also assessed.,At study end, improvements from baseline in 1-hour postdose FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC or ACL400/FOR6 FDC compared with aclidinium (108 mL and 87 mL, respectively; p < 0.0001).,Improvements in trough FEV1 were significantly greater in patients treated with ACL400/FOR12 FDC versus formoterol (45 mL; p = 0.0102), a numerical improvement of 26 mL in trough FEV1 over formoterol was observed with ACL400/FOR6 FDC.,Significant improvements in both SGRQ total and TDI focal scores were observed in the ACL400/FOR12 FDC group at study end (p < 0.0001), with differences over placebo exceeding the minimal clinically important difference of ≥4 points and ≥1 unit, respectively.,All treatments were well tolerated, with safety profiles of the FDCs similar to those of the monotherapies.,Treatment with twice-daily aclidinium 400 μg/formoterol 12 μg FDC provided rapid and sustained bronchodilation that was greater than either monotherapy; clinically significant improvements in dyspnea and health status were evident compared with placebo.,Aclidinium/formoterol FDC may be an effective and well tolerated new treatment option for patients with COPD.,Clinicaltrials.gov NCT01437397.,*Registered trademarks of Almirall S.A., Barcelona, Spain; for use within the US as Pressair® and Genuair® within all other licensed territories.,The online version of this article (doi:10.1186/s12931-014-0123-0) contains supplementary material, which is available to authorized users. | 1 |
The degree to which symptoms such as dyspnea affect patients with COPD is individualized.,To address the gap between clinical symptom measures and self-perceived disease burden, we investigated the symptom status of adult patients with COPD and followed with an administrative claims analysis of health care resource utilization and costs.,This was a hybrid US observational study consisting of a cross-sectional patient survey followed by a retrospective analysis of administrative claims data.,The primary COPD symptom measures were the modified Medical Research Council (mMRC) Dyspnea scale and the COPD Assessment Test (CAT).,A total of 673 patients completed the survey.,Of these, 65% reported mMRC grades 0-1 (low symptomatology) and 35% reported mMRC grades 2-4 (high symptomatology); 25% reported CAT score <10 (low symptomatology) and 75% reported CAT score ≥10 (high symptomatology).,More patients with high symptomatology (by either measure) had at least one COPD-related inpatient hospitalization, emergency room visit, physician office visit, or other outpatient services, and filled at least one COPD-related prescription medication vs patients with low symptomatology.,COPD-related costs were higher for patients with high symptomatology than patients with low symptomatology.,In a multivariate analysis, COPD-related costs were also higher in patients reporting severe symptoms.,Patients with high COPD symptomatology utilized more health care resources and had higher COPD-related health care costs during the 6-month post-survey period than patients with low symptomatology. | As lung function declines rapidly in the early stages of chronic obstructive pulmonary disease (COPD), the effects of bronchodilators in patients with moderate disease and those who have not previously received maintenance therapy are of interest.,OTEMTO® 1 and 2 were two replicate, 12-week, Phase III studies investigating the benefit of tiotropium + olodaterol on lung function and quality of life in patients with moderate to severe disease.,Post hoc analyses were performed to assess the benefits for patients according to disease severity and treatment history.,Four subgroup analyses were performed: Global initiative for chronic Obstructive Lung Disease (GOLD) 2/3, GOLD A/B/C/D, treatment naive/not treatment naive and receiving inhaled corticosteroids (ICS) at baseline/not receiving ICS at baseline.,Primary end points were change in forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h response, change in trough FEV1 and St George’s Respiratory Questionnaire (SGRQ) total score.,Transition Dyspnoea Index (TDI) focal score was a secondary end point, and SGRQ and TDI responder analyses were further end points; all were assessed at 12 weeks.,In all subgroups, patients receiving tiotropium + olodaterol responded better overall than those receiving tiotropium monotherapy.,Improvements with tiotropium + olodaterol over placebo or tiotropium monotherapy were noted across GOLD 2/3 and GOLD A/B/C/D; however, improvements in SGRQ total score were most evident in the GOLD B subgroup.,Moreover, lung-function outcomes were generally greater in those patients who had been receiving previous long-acting bronchodilator and/or ICS maintenance treatment.,These data suggest that tiotropium + olodaterol should be considered as a treatment option in patients with moderate COPD who are initiating maintenance therapy, as well as those with more severe disease.,ClinicalTrials.gov: NCT01964352 and NCT02006732.,The online version of this article (doi:10.1186/s12931-016-0387-7) contains supplementary material, which is available to authorized users. | 1 |
Pulmonary epithelial cells are widely considered to be the first line of defence in the lung and are responsible for coordinating the innate immune response to injury and subsequent repair.,Consequently, epithelial cells communicate with multiple cell types including immune cells and fibroblasts to promote acute inflammation and normal wound healing in response to damage.,However, aberrant epithelial cell death and damage are hallmarks of pulmonary disease, with necrotic cell death and cellular senescence contributing to disease pathogenesis in numerous respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and coronavirus disease (COVID)-19.,In this review, we summarise the literature that demonstrates that epithelial damage plays a pivotal role in the dysregulation of the immune response leading to tissue destruction and abnormal remodelling in several chronic diseases.,Specifically, we highlight the role of epithelial-derived damage-associated molecular patterns (DAMPs) and senescence in shaping the immune response and assess their contribution to inflammatory and fibrotic signalling pathways in the lung. | Chronic obstructive pulmonary disease (COPD) is the leading cause of respiratory mortality worldwide.,Genetic risk loci provide novel insights into disease pathogenesis.,We performed a genome-wide association study in 35,735 cases and 222,076 controls from the UK Biobank and additional studies from the International COPD Genetics Consortium.,We identified 82 loci with P-value < 5 × 10−8; 47 were previously described in association with either COPD or population-based lung function.,Of the remaining 35 novel loci, 13 were associated with lung function in 79,055 individuals from the SpiroMeta consortium.,Using gene expression and regulation data, we identified enrichment for loci in lung tissue, smooth muscle and several lung cell types.,We found 14 COPD loci shared with either asthma or pulmonary fibrosis.,COPD genetic risk loci clustered into groups of quantitative imaging features and comorbidity associations.,Our analyses provide further support to the genetic susceptibility and heterogeneity of COPD. | 1 |
Two replicate, double-blind, 6-week, incomplete-crossover studies (MORACTO 1 and 2) assessed the effects of tiotropium/olodaterol on inspiratory capacity and exercise endurance time in patients with moderate to severe chronic obstructive pulmonary disease.,For each patient, four of five treatments were administered once daily for 6 weeks, with a 21-day washout between treatments: tiotropium/olodaterol 2.5/5 µg or 5/5 µg, tiotropium 5 µg, olodaterol 5 µg or placebo, all via the Respimat inhaler.,Primary outcomes were inspiratory capacity prior to exercise and exercise endurance time during constant work-rate cycle ergometry to symptom limitation at 75% of peak incremental work rate after 6 weeks (2 h post-dose).,295 and 291 patients were treated in MORACTO 1 and 2, respectively.,Tiotropium/olodaterol 2.5/5 and 5/5 µg provided significant improvements in inspiratory capacity versus placebo and monotherapies (p<0.0001), and significant improvements in exercise endurance time versus placebo (p<0.0001).,Intensity of breathing discomfort was reduced following both doses of tiotropium/olodaterol versus placebo (p<0.0001).,Once-daily tiotropium/olodaterol yielded improvements in lung hyperinflation versus placebo and statistically significant improvements versus monotherapies.,Tiotropium/olodaterol also showed improvements in dyspnoea and exercise tolerance versus placebo but not consistently versus monotherapies.,T/O reduces lung hyperinflation in COPD versus T, O or placebo and increases exercise endurance versus placebohttp://ow.ly/ml3G307XW6a | Reducing rescue medication use is a guideline-defined goal of asthma treatment, however, little is known about the validity of rescue medicine use as a marker of symptoms in chronic obstructive pulmonary disease (COPD).,To improve patient outcomes, greater insight is needed into the relationship between rescue medication use and alternative COPD outcomes.,A systematic search of electronic databases (Embase®, MEDLINE® and Cochrane CENTRAL) was conducted from database start to 26 May, 2015.,Studies of bronchodilator therapy with a duration of ≥24 weeks were included if they reported either mean change from baseline (CFB) in rescue medication use in puffs/day or % rescue-free days (%RFD), and at least one other COPD endpoint.,Correlation and meta-regression analyses were undertaken to test the association between rescue medication use and other COPD outcomes using weighted means (weights proportional to the sample size of the treatment group) and unweighted means (equal weight for each treatment group).,Each association was assessed at 6 months and study end.,Forty-six studies involving 46,531 patients provided mean data from 145 treatment groups for evaluation.,Changes in both measures of rescue medication use were correlated with changes in trough forced expiratory volume in one second ([FEV1]; Pearson correlation coefficients |r| ≥ 0.63; p < 0.0001) and with St George’s Respiratory Questionnaire (SGRQ) score (|r| ≥ 0.70; p < 0.0001) at study end.,Change in rescue medication use in puffs/day during the study correlated with annualized rates of moderate/severe exacerbations at 6 months and study end (both r = 0.66; p ≤ 0.0028).,CFB in puffs/day was not well correlated with Transition Dyspnoea Index (TDI), but %RFD did correlate with TDI score at 6 months and study end (both r = 0.69; p < 0.0001).,The values for CFB in puffs/day corresponding to the proposed minimal clinically important differences for trough FEV1 and SGRQ score were -1.3 and -0.6 puffs/day, respectively.,A -1.0 puffs/day CFB in rescue use corresponded to a change of 0.26 events/patient-year in moderate/severe exacerbations.,This analysis provides clear evidence of associations at a patient group level between rescue medication use and other clinically important COPD outcomes.,The online version of this article (doi:10.1186/s12931-017-0566-1) contains supplementary material, which is available to authorized users. | 1 |
Adherence to treatment is key to achieve desired outcomes.,In COPD, adherence is generally suboptimal and is impaired by treatment complexity.,To estimate the clinical and economic impact of an improvement in treatment adherence due to an increased use of once-daily single-inhaler triple therapy (SITT) in patients with COPD.,A 7-state Markov model with monthly cycles was developed.,Patients with moderate-to-very severe COPD, for whom triple therapy is indicated, were included.,Outcomes and costs were estimated and compared for two scenarios: current distribution of adherent patients treated with multiple inhaler triple therapies (MITT) vs a potential scenario where patients shifted to once-daily SITT.,In the potential scenario, adherence improvement due to once-daily SITT attributes was estimated.,Costing was based on the Spanish National Health System (NHS) perspective (€2019).,A 3-year time horizon was defined considering a 3% discount rate for both costs and outcomes.,A target population of 185,111 patients with moderate-to-very severe COPD currently treated with MITT was estimated.,A 20% increase in the use of once-daily SITT in the potential scenario raised adherence up to 52%.,This resulted in 6835 exacerbations and 532 deaths avoided, with 775 LYs and 594 QALYs gained.,Total savings reached €7,082,105.,Exacerbation reduction accounted for 61.8% (€4,378,201) of savings.,Increasing the use of once-daily SITT in patients with moderate-to-very severe COPD treated with triple therapy would be associated with an improvement in adherence, a reduction of exacerbations and deaths, and cost savings for the Spanish NHS. | Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD).,However, choice of parameters and score complexity restrict clinical applicability.,Our aim was to provide and validate a simplified COPD risk index independent of lung function.,The PROMISE study (n=530) was used to develop a novel prognostic index.,Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality.,External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988).,Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C.,It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05).,Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively).,External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05).,The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk.,The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung functionhttp://ow.ly/XFBox | 1 |
Comorbidities are frequent in chronic obstructive pulmonary disease (COPD) and significantly impact on patients’ quality of life, exacerbation frequency, and survival.,There is increasing evidence that certain diseases occur in greater frequency amongst patients with COPD than in the general population, and that these comorbidities significantly impact on patient outcomes.,Although the mechanisms are yet to be defined, many comorbidities likely result from the chronic inflammatory state that is present in COPD.,Common problems in the clinical management of COPD include recognizing new comorbidities, determining the impact of comorbidities on patient symptoms, the concurrent treatment of COPD and comorbidities, and accurate prognostication.,The majority of comorbidities in COPD should be treated according to usual practice, and specific COPD management is infrequently altered by the presence of comorbidities.,Unfortunately, comorbidities are often under-recognized and under-treated.,This review focuses on the epidemiology of ten major comorbidities in patients with COPD.,Further, we emphasize the clinical impact upon prognosis and management considerations.,This review will highlight the importance of comorbidity identification and management in the practice of caring for patients with COPD. | Patients with chronic obstructive pulmonary disease (COPD) present with a variety of symptoms and pathological consequences.,Although primarily viewed as a respiratory disease, COPD has both pulmonary and extrapulmonary effects, which have an impact on many aspects of physical, emotional, and mental well-being.,Traditional assessment of COPD relies heavily on measuring lung function, specifically forced expiratory volume in 1 second (FEV1).,However, the evidence suggests that FEV1 is a relatively poor correlate of symptoms such as breathlessness and the impact of COPD on daily life.,Furthermore, many consequences of the disease, including anxiety and depression and the ability to perform daily activities, can only be described and reported reliably by the patient.,Thus, in order to provide a comprehensive view of the effects of interventions in clinical trials, it is essential that spirometry is accompanied by assessments using patient-reported outcome (PRO) instruments.,We provide an overview of patient-reported outcome concepts in COPD, such as breathlessness, physical functioning, and health status, and evaluate the tools used for measuring these concepts.,Particular attention is given to the newly developed instruments emerging in response to recent regulatory guidelines for the development and use of PROs in clinical trials.,We conclude that although data from the development and validation of these new PRO instruments are emerging, to build the body of evidence that supports the use of a new instrument takes many years.,Furthermore, new instruments do not necessarily have better discriminative or evaluative properties than older instruments.,The development of new PRO tools, however, is crucial, not only to ensure that key COPD concepts are being reliably measured but also that the relevant treatment effects are being captured in clinical trials.,In turn, this will help us to understand better the patient’s experience of the disease. | 1 |
To identify factors that hinder discussions regarding chronic obstructive pulmonary disease (COPD) between primary care physicians (PCPs) and their patients in Sweden.,Primary health care centres (PHCCs) in Stockholm, Sweden.,A total of 59 PCPs.,Semi-structured individual and focus-group interviews between 2012 and 2014.,Data were analysed inspired by grounded theory methods (GTM).,Time-pressured patient-doctor consultations lead to deprioritization of COPD.,During unscheduled visits, deprioritization resulted from focusing only on acute health concerns, while during routine care visits, COPD was deprioritized in multi-morbid patients.,The reasons PCPs gave for deprioritizing COPD are: “Not becoming aware of COPD”, “Not becoming concerned due to clinical features”, “Insufficient local routines for COPD care”, “Negative personal attitudes and views about COPD”, “Managing diagnoses one at a time”, and “Perceiving a patient’s motivation as low’’.,De-prioritization of COPD was discovered during PCP consultations and several factors were identified associated with time constraints and multi-morbidity.,A holistic consultation approach is suggested, plus extended consultation time for multi-morbid patients, and better documentation and local routines.,Key pointsUnder-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Under-diagnosis and insufficient management of chronic obstructive pulmonary disease (COPD) are common in primary health care.,A patient-doctor consultation offers a key opportunity to identify and provide COPD care.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD.,Time pressure, due to either high number of patients or multi-morbidity, leads to omission or deprioritization of COPD during consultation.,Deprioritization occurs due to lack of awareness, concern, and local routines, negative personal views, non-holistic consultation approach, and low patient motivation.,Better local routines, extended consultation time, and a holistic approach are needed when managing multi-morbid patients with COPD. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Self-treatment of acute exacerbations of COPD with antibiotics and/or oral corticosteroids has emerged as a promising strategy to reduce hospitalization rates, mortality and health costs.,However, for reasons little understood, the effect of self-treatment, particularly when not part of comprehensive self-management programs, remains unclear.,Therefore, this study aims to get insight into the patients’ perspective on self-treatment of acute exacerbations of COPD, focusing specifically on how patients decide for the right moment to start treatment with antibiotics and/or oral corticosteroids, what they consider important when making this decision and aspects which might interfere with successful implementation.,We interviewed 19 patients with chronic obstructive pulmonary disease using qualitative semi-structured interviews, and applied thematic analysis for data analysis.,Patients were well equipped with experiential knowledge to recognize and promptly respond to worsening COPD symptoms.,Worries regarding potential adverse effects of antibiotics and oral corticosteroids played an important role in the decision to start treatment and could result in hesitation to start treatment.,Although self-treatment represented a practical and appreciated option for some patients with predictable symptom patterns and treatment effect, all patients favoured assistance from a medical professional when their perceived competence reached its limits.,However, a feeling of obligation to succeed with self-treatment or distrust in their doctors or the health care system could keep patients from timely help seeking.,COPD patients regard self-treatment of exacerbations with antibiotics and/or oral corticosteroids as a valuable alternative.,How they engage in self-treatment depends on their concerns regarding the medications’ adverse effects as well as on their understanding of and preferences for self-treatment as a means of health care.,Caregivers should address these perspectives in a collaborative approach when offering COPD patients the opportunity for self-treatment of exacerbations.,The online version of this article (doi:10.1186/s12875-017-0582-8) contains supplementary material, which is available to authorized users. | Effective self-management in chronic obstructive pulmonary disease (COPD) is crucial to reduce hospital admissions and improve outcomes for patients.,This includes early detection and treatment of exacerbations by patients themselves.,To explore patients’ current understanding and experience of managing and identifying COPD exacerbations at home.,A qualitative, interview-based study was carried out in patients’ homes.,Interviews were audio-recorded, transcribed and analysed using a grounded theory approach.,Forty-four patients (17 women, 27 men; age range 55-85 years), with moderate-to-very-severe COPD, were recruited to the interview study from primary and secondary care settings in Oxford, UK, during 2012-2013.,Patients identified exacerbations on the basis of measurable, ‘visible’ symptoms, such as cough and sputum and ‘invisible’ symptoms, such as chest sensations and bodily knowledge.,Most patients seemed to use a combination of these approaches when identifying exacerbations, according to the symptoms that had the most impact on their well-being.,Patients used additional self-management strategies during an exacerbation, such as self-medication (antibiotics and steroids) and monitored their recovery.,Contact with health-care professionals usually occurred when patients felt no longer able to manage themselves.,Patients use both assessment of objective biomarkers, which are aligned with medical knowledge, and subjective symptoms based on their experience, to identify and manage exacerbations of COPD.,Health-care professionals and clinicians should acknowledge this ‘expert patient’ knowledge and integrate this into patients’ care plans to facilitate early recognition and treatment of exacerbations. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | Patients with COPD have frequent exacerbations.,The role of respiratory viral infection is just emerging.,We wished to determine prospectively the incidence of viral infection in exacerbated and stable COPD patients as well as smokers who do not have airways obstruction.,Stable and exacerbated COPD patients were recruited along with a group of patients who had smoked but who did not have any airways obstruction.,Spirometry was performed and sputum specimens were tested for a range of 12 different respiratory viruses using PCR.,One hundred and thirty-six patients with exacerbations of COPD, 68 stable COPD patients and 16 non-obstructed smokers were recruited.,A respiratory virus was detected in 37% of exacerbations, 12% of stable COPD patients and 12% of non-obstructed smokers, p < 0.0005.,Rhinovirus was most frequently detected.,The symptom of fever was associated with virus detection, p < 0.05.,Infection with more than one virus was only found in the exacerbated COPD patients.,Respiratory viral infection is associated with exacerbations of COPD.,Rhinovirus was the most common infecting agent identified and in two cases human metapneumovirus was also detected.,Dual infections were only seen amongst those patients admitted to hospital with acute exacerbations of COPD.,Viruses were more commonly detected in those with more severe airways disease. | 1 |
This cohort study of patients with chronic obstructive pulmonary disease (COPD) was performed to evaluate the status of inhaled corticosteroid (ICS) prescriptions following the 2017 revision of the Global Initiative for Chronic Obstructive Lung Disease guidelines.,A total of 1144 patients from the Korean Obstructive Lung Disease and Korea Chronic Obstructive Pulmonary Disorders Subgroup Study cohorts, with final follow-up visits completed between 2017 and 2018, were analyzed.,Features indicative of ICS usage were as follows: a history of asthma, blood eosinophils of ≥300 cells/μl, or ≥ 2 exacerbations in the year prior to enrollment.,Among baseline ICS users, we compared annual total and severe exacerbation rates, based on ICS continuation or withdrawal.,ICS-containing regimens were prescribed to 46.3% of the enrolled of patients in 2014; this decreased to 38.8% in 2017, and long-acting dual bronchodilators were used instead.,Among ICS users in 2017, 47.5% did not exhibit features indicative of ICS usage; 478 used ICS at baseline, and ICS was withdrawn in 77 (16.1%) during the study period.,The proportion of patients with asthma and the baseline annual exacerbation rate were greater in the ICS withdrawal groinup than in the ICS continued group (56.6% vs. 41%, p = 0.01; 0.79 vs.,0.53, p < 0.001).,Annual exacerbation rates during the follow-up period were similar between the ICS-withdrawal and ICS -continued groups (0.48 vs.,0.47, p = 0.84); however, former exhibited a significantly higher rate of severe exacerbation (0.22 vs.,0.12, p = 0.03).,Prescriptions of ICS to treat COPD decreased with increased use of long-acting dual bronchodilators.,ICS withdrawal might impact severe exacerbation; the potential risks and benefits of withdrawing ICS should therefore be considered based on patients’ characteristics. | COPD affects over 13 million Americans, and accounts for over half a million hospitalizations annually.,The Hospital Readmission Reduction Program, established by the Affordable Care Act requires the Centers for Medicare and Medicaid Services to reduce payments to hospitals with excess readmissions for COPD as of 2015.,This study sought to develop a predictive readmission scale to identify COPD patients at higher readmission risk.,Demographic and clinical data on 339,389 patients from New York and California (derivation cohort) and 258,113 patients from Washington and Florida (validation cohort) were abstracted from the State Inpatient Database (2006-2011), and the Readmission After COPD Exacerbation (RACE) Scale was developed to predict 30-day readmission risk.,Thirty-day COPD readmission rates were 7.54% for the derivation cohort and 6.70% for the validation cohort.,Factors including age 40-65 years (odds ratio [OR] 1.17; 95% CI, 1.12-1.21), male gender (OR 1.16; 95% CI, 1.13-1.19), African American (OR 1.11; 95% CI, 1.06-1.16), 1st income quartile (OR 1.10; 95% CI, 1.06-1.15), 2nd income quartile (OR 1.06; 95% CI, 1.02-1.10), Medicaid insured (OR 1.83; 95% CI, 1.73-1.93), Medicare insured (OR 1.45; 95% CI, 1.38-1.52), anemia (OR 1.05; 95% CI, 1.02-1.09), congestive heart failure (OR 1.06; 95% CI, 1.02-1.09), depression (OR 1.18; 95% CI, 1.14-1.23), drug abuse (OR 1.17; 95% CI, 1.09-1.25), and psychoses (OR 1.19; 95% CI, 1.13-1.25) were independently associated with increased readmission rates, P<0.01.,When the devised RACE scale was applied to both cohorts together, it explained 92.3% of readmission variability.,The RACE Scale reliably predicts an individual patient’s 30-day COPD readmission risk based on specific factors present at initial admission.,By identifying these patients at high risk of readmission with the RACE Scale, patient-specific readmission-reduction strategies can be implemented to improve patient care as well as reduce readmissions and health care expenditures. | 1 |
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality in the United States.,Exacerbations- acute worsening of COPD symptoms-can be mild to severe in nature.,Increased healthcare resource use is common among patients with frequent exacerbations, and exacerbations are a major cause of the high 30-day hospital readmission rates associated with COPD.,This review provides a concise overview of the literature regarding the impact of COPD exacerbations on both the patient and the healthcare system, the recommendations for pharmacologic management of COPD, and the strategies employed to improve patient care and reduce hospitalizations and readmissions.,COPD exacerbations significantly impact patients’ health-related quality of life and disease progression; healthcare costs associated with severe exacerbation-related hospitalization range from $7,000 to $39,200.,Timely and appropriate maintenance pharmacotherapy, particularly dual bronchodilators for maximizing bronchodilation, can significantly reduce exacerbations in patients with COPD.,Additionally, multidisciplinary disease-management programs include pulmonary rehabilitation, follow-up appointments, aftercare, inhaler training, and patient education that can reduce hospitalizations and readmissions for patients with COPD.,Maximizing bronchodilation by the appropriate use of maintenance therapy, together with multidisciplinary disease-management and patient education programs, offers opportunities to reduce exacerbations, hospitalizations, and readmissions for patients with COPD. | COPD symptoms show a diurnal variability.,However, morning and night variability has generally not been taken into consideration in disease management plans.,The aims of this study were to cross-sectionally assess morning and night symptom prevalence and correlation with health status and disease severity in COPD, and to determine to what extent they could predict longitudinal outcomes, exacerbations and health status.,A further aim is to explore whether the CCQ is able to depict this morning/night symptomatology.,We included 2,269 primary care COPD patients (58% male, 49% current smokers, with a mean age of 65±11 years) from a Dutch Asthma/COPD service.,Spirometry, patient history, the Clinical COPD Questionnaire(CCQ) and the Asthma Control Questionnaire(ACQ) were assessed; we used the latter to evaluate morning (question 2) and night symptoms (question 1).,A total of 1159 (51.9%) patients reported morning symptoms (ACQ question 2>0) and 879 (39.4%) had night complaints (ACQ question 1>0).,Patients with morning/night symptoms were mostly smokers and had on average poorer lung function, higher CCQ scores and used more rescue inhalers (P<0.0001).,Patients using long-acting muscarinic antagonists (LAMAs) had less night symptoms, showing a possible favourable effect.,Only a small proportion of stable or slightly unstable patients (CCQ total scores <2) had severe morning symptoms (ACQ 2⩾4: n=19, 1.1%) or severe night symptoms (ACQ 1⩾4: n=11, 0.7%).,Night symptoms seemed to predict future exacerbations; however, baseline exacerbations were the strongest predictors (n=346, OR:4.13, CI: 2.45−6.95, P<0.000).,Morning symptoms increased the odds of poor health status at follow-up (n=346, OR:12.22, CI:4.76−31.39, P<0.000).,Morning and night symptoms in COPD patients are common, and they are associated with poor health status and predicted future exacerbations.,Our study showed that patients with morning/night symptoms have higher scores in CCQ, and therefore we do not really miss patients with high morning/night symptomatology when we only measure CCQ.,Severe morning symptoms predicted worsening of COPD health status. | 1 |
Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD).,However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.,We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.,In healthy subjects Firmicutes, Bacteroidetes and Actinobacteria were the major phyla constituting 88% of the total reads, and Streptococcus, Veillonella, Prevotella, Actinomyces and Rothia were the dominant genera.,Haemophilus formed only 3% of the healthy microbiome.,In contrast, Proteobacteria was the most dominant phylum accounting for 50% of the microbiome in COPD subjects, with Haemophilus and Moraxella at genus level contributing 25 and 3% respectively.,There were no differences in the microbiome profile within healthy and COPD subgroups when stratified based on smoking history.,Principal coordinate analysis on operational taxonomic units showed two distinct clusters, representative of healthy and COPD subjects (PERMANOVA, p = 0·001).,The healthy and COPD sputum microbiomes are distinct and independent of smoking history.,Our results underline the important role for Gammaproteobacteria in COPD. | There has been increasing interest in the use of newer, culture-independent techniques to study the airway microbiome of COPD patients.,We investigated the relationships between the three common potentially pathogenic microorganisms (PPMs) Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis, as detected by quantitative PCR (qPCR), and inflammation and health status in stable patients in the London COPD cohort.,We prospectively collected sputum, serum and plasma samples for analysis of airway bacterial presence and load, and airway and systemic inflammation from 99 stable COPD patients between January 2011 and October 2012.,Health status was measured with St George’s Respiratory Questionnaire and COPD Assessment Test.,Airway inflammation and plasma fibrinogen, but not C-reactive protein, were greater in samples with PPM detection (p < 0.001, p = 0.049 and p = 0.261, respectively).,Increasing total bacterial load was associated with increasing airway (p < 0.01) but not systemic inflammation (p > 0.05).,Samples with high total bacterial loads had significantly higher airway inflammation than both samples without PPM detection and those with lower loads.,Haemophilus influenzae presence was associated with significantly higher levels of airway but not systemic inflammation for all given pathogen loads (p < 0.05), and was significantly greater than with other PPMs.,No association was observed between inflammation and health status (p > 0.05).,Airway and systemic inflammation, as measured by fibrinogen, is greater in stable COPD patients with PPMs detected using the culture-independent qPCR technique.,The airway, but not systemic inflammatory response, appears to have a total pathogen-load threshold and appears attributable to Haemophilus influenzae.,However, discordance between inflammation and health status was observed.,The online version of this article (doi:10.1186/s12931-014-0114-1) contains supplementary material, which is available to authorized users. | 1 |
Chronic obstructive pulmonary disease (COPD) is a debilitating disease affecting patients in daily life, both physically and emotionally.,Symptoms such as dyspnea and muscle fatigue, lead to exercise intolerance, which, together with behavioral issues, trigger physical inactivity, a key feature of COPD.,Physical inactivity is associated with adverse clinical outcomes, including hospitalization and all-cause mortality.,Increasing activity levels is crucial for effective management strategies and could lead to improved long-term outcomes.,In this review we summarize objective and subjective instruments for evaluating physical activity and focus on interventions such as pulmonary rehabilitation or bronchodilators aimed at increasing activity levels.,To date, only limited evidence exists to support the effectiveness of these interventions.,We suggest that a multimodal approach comprising pulmonary rehabilitation, pharmacotherapy, and counselling programs aimed at addressing emotional and behavioural aspects of COPD may be an effective way to increase physical activity and improve health status in the long term. | GSK233705 is an inhaled, long-acting muscarinic antagonist in development for the treatment of chronic obstructive pulmonary disease (COPD).,This study was performed to see if the addition of GSK233705 to salmeterol would provide greater bronchodilation than salmeterol or tiotropium alone in COPD.,In an incomplete-block, three-period, crossover design, dually responsive patients received three of the following five treatments: GSK233705 20 μg plus salmeterol 50 μg twice-daily; GSK233705 50 μg plus salmeterol 50 μg twice-daily; salmeterol 50 μg or placebo, each twice-daily; and tiotropium 18 μg or placebo once-daily for 7 days.,Each treatment period was separated by a 14-day washout.,The primary efficacy endpoint was morning (trough) forced expiratory volume in 1 second (FEV1) on Day 8, following 7 days of treatment.,Secondary endpoints included pulmonary function, plethysmography, pharmacokinetics of GSK233705 and salmeterol, adverse events (AEs), electrocardiograms (ECGs), vital signs, and laboratory parameters.,A total of 47 patients were randomized.,The mean % predicted normal postbronchodilator FEV1 was 55% at screening.,Compared with placebo (n = 24), the adjusted mean change from baseline in trough FEV1 on Day 8 was 215 mL higher with GSK233705 20 μg + salmeterol (n = 23) and 203 mL higher with GSK233705 50 μg + salmeterol (n = 27), whereas with salmeterol (n = 27) and tiotropium (n = 28) the changes were 101 mL and 118 mL higher, respectively.,The primary efficacy results were supported by the results from the other secondary lung function assessments.,AEs were reported by similar proportions of patients across the treatment groups, with headache the most frequently reported treatment-related AE reported by one subject receiving each of GSK233705 20 μg + salmeterol, tiotropium, and placebo.,No significant differences were seen in vital signs, ECGs, or laboratory parameters between the groups.,The addition of GSK233705 to salmeterol in partially reversible COPD patients resulted in greater bronchodilation than salmeterol or tiotropium alone and was well tolerated. | 1 |
Changes in microbial community composition in the lung of patients suffering from moderate to severe COPD have been well documented.,However, knowledge about specific microbiome structures in the human lung associated with CT defined abnormalities is limited.,Bacterial community composition derived from brush samples from lungs of 16 patients suffering from different CT defined subtypes of COPD and 9 healthy subjects was analyzed using a cultivation independent barcoding approach applying 454-pyrosequencing of 16S rRNA gene fragment amplicons.,We could show that bacterial community composition in patients with changes in CT (either airway or emphysema type changes, designated as severe subtypes) was different from community composition in lungs of patients without visible changes in CT as well as from healthy subjects (designated as mild COPD subtype and control group) (PC1, Padj = 0.002).,Higher abundance of Prevotella in samples from patients with mild COPD subtype and from controls and of Streptococcus in the severe subtype cases mainly contributed to the separation of bacterial communities of subjects.,No significant effects of treatment with inhaled glucocorticoids on bacterial community composition were detected within COPD cases with and without abnormalities in CT in PCoA.,Co-occurrence analysis suggests the presence of networks of co-occurring bacteria.,Four communities of positively correlated bacteria were revealed.,The microbial communities can clearly be distinguished by their associations with the CT defined disease phenotype.,Our findings indicate that CT detectable structural changes in the lung of COPD patients, which we termed severe subtypes, are associated with alterations in bacterial communities, which may induce further changes in the interaction between microbes and host cells.,This might result in a changed interplay with the host immune system. | Oxidative stress occurs when free radicals and other reactive species overwhelm the availability of antioxidants.,Reactive oxygen species (ROS), reactive nitrogen species, and their counterpart antioxidant agents are essential for physiological signaling and host defense, as well as for the evolution and persistence of inflammation.,When their normal steady state is disturbed, imbalances between oxidants and antioxidants may provoke pathological reactions causing a range of nonrespiratory and respiratory diseases, particularly chronic obstructive pulmonary disease (COPD).,In the respiratory system, ROS may be either exogenous from more or less inhalative gaseous or particulate agents such as air pollutants, cigarette smoke, ambient high-altitude hypoxia, and some occupational dusts, or endogenously generated in the context of defense mechanisms against such infectious pathogens as bacteria, viruses, or fungi.,ROS may also damage body tissues depending on the amount and duration of exposure and may further act as triggers for enzymatically generated ROS released from respiratory, immune, and inflammatory cells.,This paper focuses on the general relevance of free radicals for the development and progression of both COPD and pulmonary emphysema as well as novel perspectives on therapeutic options.,Unfortunately, current treatment options do not suffice to prevent chronic airway inflammation and are not yet able to substantially alter the course of COPD.,Effective therapeutic antioxidant measures are urgently needed to control and mitigate local as well as systemic oxygen bursts in COPD and other respiratory diseases.,In addition to current therapeutic prospects and aspects of genomic medicine, trending research topics in COPD are presented. | 1 |
Rationale: Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches.,Objectives: To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations.,Methods: An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.,The microbiome was analyzed using COPDMAP and AERIS as a discovery data set and BEAT-COPD as a validation data set.,Measurements and Main Results: The airway microbiome in neutrophilic COPD was heterogeneous, with two primary community types differentiated by the predominance of Haemophilus.,The Haemophilus-predominant subgroup had elevated sputum IL-1β and TNFα (tumor necrosis factor α) and was relatively stable over time.,The other neutrophilic subgroup with a balanced microbiome profile had elevated sputum and serum IL-17A and was temporally dynamic.,Patients in this state at stability were susceptible to the greatest microbiome shifts during exacerbations.,This subgroup can temporally switch to both neutrophilic Haemophilus-predominant and eosinophilic states that were otherwise mutually exclusive.,Time-series analysis on the microbiome showed that the temporal trajectories of Campylobacter and Granulicatella were indicative of intrapatient switches from neutrophilic to eosinophilic inflammation, in track with patient sputum eosinophilia over time.,Network analysis revealed distinct host-microbiome interaction patterns among neutrophilic Haemophilus-predominant, neutrophilic balanced microbiome, and eosinophilic subgroups.,Conclusions: The airway microbiome can stratify neutrophilic COPD into subgroups that justify different therapies.,Neutrophilic and eosinophilic COPD are interchangeable in some patients.,Monitoring temporal variability of the airway microbiome may track patient inflammatory status over time. | A sputum eosinophilia is observed in 10-40% of COPD subjects.,The blood eosinophil count is a biomarker of sputum eosinophilia, but whether it is associated with bronchial submucosal eosinophils is unclear.,In 20 COPD subjects and 21 controls we assessed the number of bronchial submucosal eosinophils and reticular basement membrane thickening and found these were positively correlated with the blood eosinophil percentage.,In COPD, blood eosinophils are a good biomarker of bronchial eosinophilia and remodelling. | 1 |
Guideline recommendations for chronic obstructive pulmonary disease (COPD) are based on the results of large pharmaceutically-sponsored COPD studies (LPCS).,There is a paucity of data on disease characteristics at the primary care level, while the majority of COPD patients are treated in primary care.,We aimed to evaluate the external validity of six LPCS (ISOLDE, TRISTAN, TORCH, UPLIFT, ECLIPSE, POET-COPD) on which current guidelines are based, in relation to primary care COPD patients, in order to inform future clinical practice guidelines and trials.,Baseline data of seven primary care databases (n = 3508) from Europe were compared to baseline data of the LPCS.,In addition, we examined the proportion of primary care patients eligible to participate in the LPCS, based on inclusion criteria.,Overall, patients included in the LPCS were younger (mean difference (MD)-2.4; p = 0.03), predominantly male (MD 12.4; p = 0.1) with worse lung function (FEV1% MD -16.4; p<0.01) and worse quality of life scores (SGRQ MD 15.8; p = 0.01).,There were large differences in GOLD stage distribution compared to primary care patients.,Mean exacerbation rates were higher in LPCS, with an overrepresentation of patients with ≥1 and ≥2 exacerbations, although results were not statistically significant.,Our findings add to the literature, as we revealed hitherto unknown GOLD I exacerbation characteristics, showing 34% of mild patients had ≥1 exacerbations per year and 12% had ≥2 exacerbations per year.,The proportion of primary care patients eligible for inclusion in LPCS ranged from 17% (TRISTAN) to 42% (ECLIPSE, UPLIFT).,Primary care COPD patients stand out from patients enrolled in LPCS in terms of gender, lung function, quality of life and exacerbations.,More research is needed to determine the effect of pharmacological treatment in mild to moderate patients.,We encourage future guideline makers to involve primary care populations in their recommendations. | Chronic obstructive pulmonary disease (COPD) is predicted to become a major cause of death worldwide.,Studies on the variability in the estimates of key epidemiological parameters of COPD may contribute to better assessment of the burden of this disease and to helpful guidance for future research and public policies.,In the present study, we examined differences in the main epidemiological characteristics of COPD derived from studies across countries of the European Union, focusing on prevalence, severity, frequency of exacerbations and mortality, as well as on differences between the studies' methods.,This systematic review was based on a search for the relevant literature in the Science Citation Index database via the Web of Science and on COPD mortality rates issued from national statistics.,Analysis was finally based on 65 articles and Eurostat COPD mortality data for 21 European countries.,Epidemiological characteristics of COPD varied widely from country to country.,For example, prevalence estimates ranged between 2.1% and 26.1%, depending on the country, the age group and the methods used.,Likewise, COPD mortality rates ranged from 7.2 to 36.1 per 105 inhabitants.,The methods used to estimate these epidemiological parameters were highly variable in terms of the definition of COPD, severity scales, methods of investigation and target populations.,Nevertheless, to a large extent, several recent international guidelines or research initiatives, such as GOLD, BOLD or PLATINO, have boosted a substantial standardization of methodology in data collection and have resulted in the availability of more comparable epidemiological estimates across countries.,On the basis of such standardization, severity estimates as well as prevalence estimates present much less variation across countries.,The contribution of these recent guidelines and initiatives is outlined, as are the problems remaining in arriving at more accurate COPD epidemiological estimates across European countries.,The accuracy of COPD epidemiological parameters is important for guiding decision making with regard to preventive measures, interventions and patient management in various health care systems.,Therefore, the recent initiatives for standardizing data collection should be enhanced to result in COPD epidemiological estimates of improved quality.,Moreover, establishing international guidelines for reporting research on COPD may also constitute a major contribution. | 1 |
Chronic Obstructive Pulmonary Disease is the third leading cause of death in the US, and is associated with periodic exacerbations, which account for the largest proportion of health care utilization, and lead to significant morbidity, mortality, and worsening lung function.,A subset of patients with COPD have frequent exacerbations, occurring 2 or more times per year.,Despite many interventions to reduce COPD exacerbations, there is a significant lack of knowledge in regards to their mechanisms and predisposing factors.,We describe here an important observation that defines antibody deficiency as a potential risk factor for frequent COPD exacerbations.,We report a case series of patients who have frequent COPD exacerbations, and who were found to have an underlying primary antibody deficiency syndrome.,We also report on the outcome of COPD exacerbations following treatment in a subset with of these patients with antibody deficiency.,We identified patients with COPD who had 2 or more moderate to severe exacerbations per year; immune evaluation including serum immunoglobulin levels and pneumococcal IgG titers was performed.,Patients diagnosed with an antibody deficiency syndrome were treated with either immunoglobulin replacement therapy or prophylactic antibiotics, and their COPD exacerbations were monitored over time.,A total of 42 patients were identified who had 2 or more moderate to severe COPD exacerbations per year.,Twenty-nine patients had an underlying antibody deficiency syndrome: common variable immunodeficiency (8), specific antibody deficiency (20), and selective IgA deficiency (1).,Twenty-two patients had a follow-up for at least 1 year after treatment of their antibody deficiency, which resulted in a significant reduction of COPD exacerbations, courses of oral corticosteroid use and cumulative annual dose of oral corticosteroid use, rescue antibiotic use, and hospitalizations for COPD exacerbations.,This case series identifies antibody deficiency as a potentially treatable risk factor for frequent COPD exacerbations; testing for antibody deficiency should be considered in difficult to manage frequently exacerbating COPD patients.,Further prospective studies are warranted to further test this hypothesis. | The coexistence of gastroesophageal reflux disease (GERD) and COPD has been recognized, but there has been no comprehensive evaluation of the impact of GERD on COPD-related health status and patient-centered outcomes.,Cross-sectional and longitudinal study of 4,483 participants in the COPDGene cohort who met GOLD criteria for COPD.,Physician-diagnosed GERD was ascertained by questionnaire.,Clinical features, spirometry and imaging were compared between COPD subjects without versus with GERD.,We evaluated the relationship between GERD and symptoms, exacerbations and markers of microaspiration in univariate and multivariate models.,Associations were additionally tested for the confounding effect of covariates associated with a diagnosis of GERD and the use of proton-pump inhibitor medications (PPIs).,To determine whether GERD is simply a marker for the presence of other conditions independently associated with worse COPD outcomes, we also tested models incorporating a GERD propensity score.,GERD was reported by 29% of subjects with female predominance.,Subjects with GERD were more likely to have chronic bronchitis symptoms, higher prevalence of prior cardiovascular events (combined myocardial infarction, coronary artery disease and stroke 21.3% vs.,13.4.0%, p < 0.0001).,Subjects with GERD also had more severe dyspnea (MMRC score 2.2 vs.,1.8, p < 0.0001), and poorer quality of life (QOL) scores (St.,George’s Respiratory Questionnaire (SGRQ) total score 41.8 vs.,34.9, p < 0.0001; SF36 Physical Component Score 38.2 vs.,41.4, p < 0.0001).,In multivariate models, a significant relationship was detected between GERD and SGRQ (3.4 points difference, p < 0.001) and frequent exacerbations at baseline (≥2 exacerbation per annum at inclusion OR 1.40, p = 0.006).,During a mean follow-up time of two years, GERD was also associated with frequent (≥2/year exacerbations OR 1.40, p = 0.006), even in models in which PPIs, GERD-PPI interactions and a GERD propensity score were included.,PPI use was associated with frequent exacerbator phenotype, but did not meaningfully influence the GERD-exacerbation association.,In COPD the presence of physician-diagnosed GERD is associated with increased symptoms, poorer QOL and increased frequency of exacerbations at baseline and during follow-up.,These associations are maintained after controlling for PPI use.,The PPI-exacerbations association could result from confounding-by-indication. | 1 |
Denominamos enfermedad pulmonar obstructiva crónica a un conjunto de procesos clínicos que tienen en común una obstrucción crónica y progresiva al flujo aéreo, salpicada de episodios de reagudización (exacerbaciones o brotes).,Estas exacerbaciones se hacen con el tiempo más frecuentes e intensas deteriorando la función pulmonar.,La principal causa de estas agudizaciones es la infección bacteriana.,Existen múltiples guías y documentos que abordan el manejo de esta patología.,Sin embargo, se centran fundamentalmente en el tratamiento durante la fase estable.,Este documento realiza un abordaje del problema de la exacerbación aguda con origen infeccioso desde una perspectiva multidisciplinar, centrándonos en el abordaje integral del proceso, y aborda la etiología, resistencias a los antimicrobianos, estudios microbiológicos, la estratificación del riesgo y el manejo terapéutico empírico inicial, antibiótico y concomitante.,Además, incluye una aproximación frente aspectos más complejos como son el manejo de poblaciones especiales (ancianos, inmunodeprimidos) o del fracaso terapéutico ante el tratamiento instaurado.,Por último, se discuten específicamente temas más controvertidos como la profilaxis de la infección o el tratamiento paliativo. | Chronic infections are associated with exacerbation in patients with chronic obstructive pulmonary disease (COPD).,The major objective of the management of these patients is the prevention and effective treatment of exacerbations.,Patients that have increased sputum production, associated with purulence and worsening shortness of breath, are the ones that will benefit from antibiotic therapy.,It is important to give the appropriate antibiotic therapy to prevent treatment failure, relapse, and the emergence of resistant pathogens.,In some patients, systemic corticosteroids are also indicated to improve symptoms.,In order to identify which patients are more likely to benefit from these therapies, clinical guidelines recommend stratifying patients based on their risk factor associated with poor outcome or recurrence.,It has been identified that patients with more severe disease, recurrent infection and presence of purulent sputum are the ones that will be more likely to benefit from this therapy.,Another approach related to disease prevention could be the use of prophylactic antibiotics during steady state condition.,Some studies have evaluated the continuous or the intermittent use of antibiotics in order to prevent exacerbations.,Due to increased bacterial resistance to antibiotics and the presence of side effects, several antibiotics have been developed to be nebulized for both treatment and prevention of acute exacerbations.,There is a need to design long-term studies to evaluate these interventions in the natural history of the disease.,The purpose of this publication is to review our understanding of the role of bacterial infection in patients with COPD exacerbation, the role of antibiotics, and future interventions. | 1 |
Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States with no effective treatment.,The current diagnostic method, spirometry, does not accurately reflect the severity of COPD disease status.,Therefore, there is a pressing unmet medical need to develop noninvasive methods and reliable biomarkers to detect early stages of COPD.,Lipids are the fundamental components of cell membranes, and dysregulation of lipids was proven to be associated with COPD.,Lipidomics is a comprehensive approach to all the pathways and networks of cellular lipids in biological systems.,It is widely used for disease diagnosis, biomarker identification, and pathology disorders detection relating to lipid metabolism.,In the current study, a total of 25 serum samples were collected from 5 normal control subjects and 20 patients with different stages of COPD according to the global initiative for chronic obstructive lung disease (GOLD) (GOLD stages I ~ IV, 5 patients per group).,After metabolite extraction, lipidomic analysis was performed using electrospray ionization mass spectrometry (ESI-MS) to detect the serum lipid species.,Later, the comparisons of individual lipids were performed between controls and patients with COPD.,Orthogonal projections to latent structures discriminant analysis (OPLS-DA) and receiver operating characteristic (ROC) analysis were utilized to test the potential biomarkers.,Finally, correlations between the validated lipidomic biomarkers and disease stages, age, FEV1% pack years and BMI were evaluated.,Our results indicate that a panel of 50 lipid metabolites including phospholipids, sphingolipids, glycerolipids, and cholesterol esters can be used to differentiate the presence of COPD.,Among them, 10 individual lipid species showed significance (p < 0.05) with a two-fold change.,In addition, lipid ratios between every two lipid species were also evaluated as potential biomarkers.,Further multivariate data analysis and receiver operating characteristic (ROC: 0.83 ~ 0.99) analysis suggest that four lipid species (AUC:0.86 ~ 0.95) and ten lipid ratios could be potential biomarkers for COPD (AUC:0.94 ~ 1) with higher sensitivity and specificity.,Further correlation analyses indicate these potential biomarkers were not affected age, BMI, stages and FEV1%, but were associated with smoking pack years.,Using lipidomics and statistical methods, we identified unique lipid signatures as potential biomarkers for diagnosis of COPD.,Further validation studies of these potential biomarkers with large population may elucidate their roles in the development of COPD. | This systematic review sought to identify the association of dietary intake and supplementation of specific polyunsaturated fatty acids with inflammation and function in people with chronic obstructive pulmonary disease (COPD).,We searched electronic databases including PubMed, CINAHL, MEDLINE, EMBASE, The Cochrane Library, ProQuest Dissertations and Theses, Scopus, Google Scholar, Trove, and WHO International Clinical Trials Registry Platform and reference lists of retrieved articles published prior to August 2014.,We considered observational studies that evaluated dietary intake of omega-3 (eicosapentaenoic acid, docosahexaenoic acid or α-linolenic acid) and/or omega-6 fatty acids (γ-linoleic acid or arachidonic acid), and experimental studies that evaluated omega-3 fatty acid supplementation (containing predominantly one or more omega-3 fatty acids) on airway and systemic inflammatory markers and/or functional capacity outcomes in people with COPD-related diagnoses.,Since statistical pooling was not possible, the findings were presented in narrative form including tables and figures to aid in data presentation when appropriate.,One 8-week randomized controlled trial conducted in 80 COPD patients in the Netherlands showed polyunsaturated fatty acid supplementation significantly improved exercise capacity compared with the control condition [between-group difference in mean peak workload was 9.7 W (2.5-17.0; P = 0.009); and mean duration was 4.3 min (0.6-7.9; P = 0.023)].,One cross-sectional study conducted in 250 COPD patients in Spain found associations of specific dietary omega-3 fatty acids with inflammation were inconsistent.,Limited evidence provides weak support for the use of omega-3 fatty acid supplementation for reducing chronic inflammation and some support for improving functional capacity in COPD patients.,There is no consistent evidence showing that low dietary intake of specific omega-3 fatty acids worsens inflammation and/or function.,More evidence is required before routinely incorporating this therapy within COPD management plans. | 1 |
Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | Chronic Obstructive Pulmonary Disease (COPD) is a chronic disease with repeated exacerbations resulting in gradual debilitation.,The quality of life has been shown to be poor in patients with COPD despite efforts to improve self-management.,However, the evidence on the benefit of self-management in COPD is conflicting.,Whether this could be due to other unmet needs of patients have not been investigated.,Therefore, we aimed to explore unmet needs of patients from both patients and doctors managing COPD.,We conducted a qualitative study with doctors and patients in Malaysia.,We used convenience sampling to recruit patients until data saturation.,Eighteen patients and eighteen doctors consented and were interviewed using a semi-structured interview guide.,The interviews were audio-recorded, transcribed verbatim and checked by the interviewers.,Data were analysed using a thematic approach.,The themes were similar for both the patients and doctors.,Three main themes emerged: knowledge and awareness of COPD, psychosocial and physical impact of COPD and the utility of self-management.,Knowledge about COPD was generally poor.,Patients were not familiar with the term chronic obstructive pulmonary disease or COPD.,The word ‘asthma’ was used synonymously with COPD by both patients and doctors.,Most patients experienced difficulties in their psychosocial and physical functions such as breathlessness, fear and helplessness.,Most patients were not confident in self-managing their illness and prefer a more passive role with doctors directing their care.,In conclusion, our study showed that knowledge of COPD is generally poor.,There was mislabelling of COPD as asthma by both patients and physicians.,This could have resulted in the lack of understanding of treatment options, outcomes, and prognosis of COPD.,The misconception that cough due to COPD was contagious, and breathlessness that resulted from COPD, had important physical and psychosocial impact, and could lead to social isolation.,Most patients and physicians did not favour self-management approaches, suggesting innovations based on self-management may be of limited benefit. | 1 |
The aetiology of acute exacerbations of COPD (AECOPD) is incompletely understood.,Understanding the relationship between chronic bacterial airway infection and viral exposure may explain the incidence and seasonality of these events.,In this prospective, observational cohort study (NCT01360398), patients with COPD aged 40-85 years underwent sputum sampling monthly and at exacerbation for detection of bacteria and viruses.,Results are presented for subjects in the full cohort, followed for 1 year.,Interactions between exacerbation occurrence and pathogens were investigated by generalised estimating equation and stratified conditional logistic regression analyses.,The mean exacerbation rate per patient-year was 3.04 (95% CI 2.63 to 3.50).,At AECOPD, the most common bacterial species were non-typeable Haemophilus influenzae (NTHi) and Moraxella catarrhalis, and the most common virus was rhinovirus.,Logistic regression analyses (culture bacterial detection) showed significant OR for AECOPD occurrence when M. catarrhalis was detected regardless of season (5.09 (95% CI 2.76 to 9.41)).,When NTHi was detected, the increased risk of exacerbation was greater in high season (October-March, OR 3.04 (1.80 to 5.13)) than low season (OR 1.22 (0.68 to 2.22)).,Bacterial and viral coinfection was more frequent at exacerbation (24.9%) than stable state (8.6%).,A significant interaction was detected between NTHi and rhinovirus presence and AECOPD risk (OR 5.18 (1.92 to 13.99); p=0.031).,AECOPD aetiology varies with season.,Rises in incidence in winter may be driven by increased pathogen presence as well as an interaction between NTHi airway infection and effects of viral infection.,Results, NCT01360398. | Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide.,Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities.,COPD exacerbations and comorbidities contribute to the overall severity in individual patients.,Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age.,Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations.,However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide.,This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale.,Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases.,All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases.,In this review, we focus on the major comorbidities that affect COPD patients.,We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs.,We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity. | 1 |
Chronic obstructive pulmonary disease (COPD) is a systemic disease.,Several long non-coding RNAs (lncRNAs) have been identified to be aberrantly expressed in COPD patients.,This study investigated the role of lncRNA cancer susceptibility candidate 2 (CASC2) in COPD, as well as its potential mechanism.,Fifty smokers with COPD and another 50 smokers without COPD were recruited.,Receiver operating characteristic curve was constructed to assess the diagnostic value of CASC2 in COPD patients.,16HBE cells were treated with cigarette smoke extract (CSE) to establish a cell model. qRT-PCR was used for the measurement of mRNA levels.,The cell viability and apoptosis were detected by using Cell Counting Kit-8 and flow cytometry assay.,Enzyme-linked immunosorbent assay was performed to detect the levels of proinflammatory cytokines.,Luciferase reporter assay was performed for the target gene analysis.,Serum CASC2 was dramatically decreased in COPD patients compared with smokers without COPD, and was positively associated with FEV1 (forced expiratory volume in one second).,Serum CASC2 was overexpressed in severe COPD patients, and had the diagnostic accuracy to distinguish COPD patients from smokers.,CASC2 overexpression alleviated CSE-induced apoptosis and inflammation in 16HBE cells.,CASC2 functions as a ceRNA of miR-18a-5p.,Upregulation of miR-18a-5p reversed the influence of CASC2 on cell apoptosis and inflammation in 16HBE cells.,IGF1 was the target gene of miR-18a-5p.,CASC2 was downregulated in COPD patients and it might be a promising biomarker for the disease diagnosis.,Overexpression of CASC2 might inhibit the bronchial epithelial cell apoptosis and inflammation via targeting miR-18a-5p/IGF1 axis.,The reviews of this paper are available via the supplemental material section. | The aim of the study was to determine the expression profile of long noncoding RNAs (lncRNAs) in CD4+ T cells from COPD patients and explore the clinical value of the lncRNAs.,First, microarray analysis was performed.,Differentially expressed lncRNAs were validated by quantitative real-time reverse transcription-PCR (qRT-PCR) in samples from 56 patients with acute exacerbations of COPD (AECOPD), 56 patients with stable COPD, and 35 healthy controls.,Meanwhile, the clinical value was tested by receiver operating characteristic curve analysis.,The functions of lncRNAs were analyzed by the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes database.,The potential target genes that might be regulated by NR-026690 and ENST00000447867 were identified by the lncRNA-mRNA network and competing endogenous RNA network.,The transcriptional expression level of rap guanine nucleotide exchange factor 3 (RAPGEF3) was tested by qRT-PCR.,The correlation of the expression between NR-026690, ENST00000447867, and RAPGEF3 was analyzed by Spearman’s correlation test.,We found that the relative expression levels of ENST00000447867 and NR-026690 in the CD4+ T cells of AECOPD patients were significantly higher than in the stable COPD patients and control subjects by microarray and qRT-PCR validation.,The transcriptional expression level of RAPGEF3 in the CD4+ T cells was significantly higher in the AECOPD group compared to the control group (P<0.01) and the stable COPD group (P<0.05).,RAPGEF3 expression was positively associated with NR-026690 (r=0.4925, P<0.01) and ENST00000447867 (r=0.4065, P<0.01).,NR-026690 and ENST00000447867 might be potential biomarkers for COPD.,They might affect RAPGEF3 as miRNA sponges to regulate COPD development. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) exhibit poor sleep quality and consider morning as the worst time of day for their symptoms.,While work has been done to characterize nighttime (NT) and early morning (EM) symptoms in various populations, the impact and factors associated with NT/EM symptoms among patients with COPD in the United States is not well understood.,Commercially insured patients aged ≥40 years with one or more medical claim for COPD and one or more pharmacy claim for COPD maintenance medication were identified from the HealthCore Integrated Research Database between September 1, 2010 and August 31, 2011.,Consenting respondents were asked whether they had COPD symptoms on at least three nights or at least three mornings during the past week.,Respondents were then either assigned to one of three symptom groups to complete the survey or excluded if their predefined group quota limit had been met.,Survey completers completed the survey with questions about COPD symptoms and other commonly used patient-reported outcome measures.,Respondents with NT/EM symptoms were asked about the frequency, severity, and impact of the symptoms on sleep, morning activities, and anxiety levels.,Among respondents with symptoms, 73.1% of respondents with NT symptoms (N=376) and 83% of respondents with EM symptoms (N=506) experienced at least three distinct types of symptoms over the past week, with cough being the most frequently reported symptom.,Approximately half of respondents with NT or EM symptoms perceived their symptoms as moderate to very severe, with a majority reporting their symptoms affected their NT sleep and morning activities, and more than half felt anxious due to their symptoms.,Multinomial logistic regression showed COPD patients with both or either NT/EM symptoms were associated with poorer health status compared to those without.,Improved disease management may reduce NT/EM symptoms and improve health status in patients with COPD. | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Elevated plasma B-type natriuretic peptide (BNP) levels and their association with heart failure have been reported in subjects with acute exacerbations of chronic obstructive pulmonary disease (AECOPD).,To examine and compare plasma BNP levels and diastolic and systolic dysfunction in subjects with AECOPD and stable chronic obstructive pulmonary disease (COPD).,In all, 87 unselected consecutive hospitalizations due to AECOPD in 61 subjects and a total of 190 consecutive subjects with stable COPD were recruited.,Plasma BNP levels were compared cross-sectionally and longitudinally.,Transthoracic echocardiographic examinations were also performed in the hospitalized subjects.,In the hospitalized subjects, the median plasma BNP level (interquartile range) was 55.4 (26.9-129.3) pg/mL and was higher than that of patients with stable COPD: 18.3 (10.0-45.3) for Global Initiative for Chronic Obstructive Lung Disease grade I; 25.8 (11.0-53.7) for grade II; 22.1 (9.1-52.6) for grade III; and 17.2 (9.6-22.9) pg/mL for grade I V, all P<0.001.,In 15 subjects studied prospectively, the median plasma BNP level was 19.4 (9.8-32.2) pg/mL before AECOPD, 72.7 (27.7-146.3) pg/mL during AECOPD, and 14.6 (12.9-39.0) pg/mL after AECOPD (P<0.0033 and P<0.0013, respectively).,Median plasma BNP levels during AECOPD were significantly higher in ten unsuccessfully discharged subjects 260.5 (59.4-555.0) than in 48 successfully discharged subjects 48.5 (24.2-104.0) pg/mL (P=0.0066).,Only 5.6% of AECOPD subjects were associated with systolic dysfunction defined as a left ventricular ejection fraction (LVEF) <50%; a further 7.4% were considered to have impaired relaxation defined as an E/A wave velocity ratio <0.8 and a deceleration time of E >240 ms.,BNP levels were weakly correlated with the E/peak early diastolic velocity of the mitral annulus (Ea) ratio (Spearman’s rank correlation coefficient =0.353, P=0.018), but they were not correlated with the LVEF (Spearman’s rank correlation coefficient =−0.221, P=0.108).,A modest elevation of plasma BNP is observed during AECOPD.,It appears that AECOPD may have an impact on plasma BNP levels that is not attributable to heart failure. | Cardiovascular disease is prevalent and frequently unrecognized in patients with chronic obstructive pulmonary disease (COPD).,NT-proBNP is an established risk factor in patients with heart failure.,NT-proBNP may also be released from the right ventricle.,Thus serum NT-proBNP may be elevated during acute exacerbations of COPD (AECOPD).,The prognostic value of NT-proBNP in patients hospitalized with AECOPD is sparsely studied.,Our objective was to test the hypothesis that NT-proBNP independently predicts long term mortality following AECOPD.,A prospective cohort study of 99 patients with 217 admissions with AECOPD.,Clinical, electrocardiographic, radiological and biochemical data were collected at index and repeat admissions and analyzed in an extended survival analysis with time-dependent covariables.,Median follow-up time was 1.9 years, and 57 patients died during follow-up.,NT-proBNP tertile limits were 264.4 and 909 pg/mL, and NT-proBNP in tertiles 1 through 3 was associated with mortality rates of 8.6, 35 and 62 per 100 patient-years, respectively (age-adjusted log-rank p<0.0001).,After adjustment for age, gender, peripheral edema, cephalization and cTnT in a multivariable survival model, the corresponding hazard ratios for dying were 2.4 (0.95-6.0) and 3.2 (1.3-8.1) (with 95% confidence intervals in parentheses, p-value for trend 0.013).,NT-proBNP is a strong and independent determinant of mortality after AECOPD. | 1 |
Recently, it was shown that chronic tobacco smoking evokes specific cellular and molecular changes in white blood cells by an excess of G protein-coupled receptor 15 (GPR15)-expressing T cells as well as a hypomethylation at DNA CpG site cg05575921 in granulocytes.,In the present study, we aimed to clarify the general usefulness of these two biomarkers as putative signs of non-cancerous change in homeostasis of the lungs.,In a clinical cohort consisting of 42 patients with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD) and pneumonia and a control cohort of 123 volunteers, the content of GPR15-expressing blood cells as well as the degree of methylation at cg05575921 were analysed by flow-cytometry and pyrosequencing, respectively.,Smoking behaviour was estimated by questionnaire and cotinine level in plasma.,Never-smoking patients could be distinguished from former and current smokers by both the proportion of GPR15-expressing T cells as well as cg05575921 methylation in granulocytes, with 100% and 97% specificity and 100% sensitivity, respectively.,However, both parameters were not affected by lung diseases.,The degrees of both parameters were not changed neither in non-smoking nor smoking patients, compared to appropriate control cohorts of volunteers.,The degree of GPR15-expressing cells among T cells as well as the methylation at cg05575921 in granulocytes in blood are both rather signs of tobacco-smoking induced systemic inflammation because they don’t indicate specifically non-cancerous pathological changes in the lungs. | Exacerbations of chronic obstructive pulmonary disease (COPD), characterized by acute deterioration in symptoms, may be due to bacterial or viral infections, environmental exposures, or unknown factors.,Exacerbation frequency may be a stable trait in COPD patients, which could imply genetic susceptibility.,Observing the genes, networks, and pathways that are up- and down-regulated in COPD patients with differing susceptibility to exacerbations will help to elucidate the molecular signature and pathogenesis of COPD exacerbations.,Gene expression array and plasma biomarker data were obtained using whole-blood samples from subjects enrolled in the Treatment of Emphysema With a Gamma-Selective Retinoid Agonist (TESRA) study.,Linear regression, weighted gene co-expression network analysis (WGCNA), and pathway analysis were used to identify signatures and network sub-modules associated with the number of exacerbations within the previous year; other COPD-related phenotypes were also investigated.,Individual genes were not found to be significantly associated with the number of exacerbations.,However using network methods, a statistically significant gene module was identified, along with other modules showing moderate association.,A diverse signature was observed across these modules using pathway analysis, marked by differences in B cell and NK cell activity, as well as cellular markers of viral infection.,Within two modules, gene set enrichment analysis recapitulated the molecular signatures of two gene expression experiments; one involving sputum from asthma exacerbations and another involving viral lung infections.,The plasma biomarker myeloperoxidase (MPO) was associated with the number of recent exacerbations.,A distinct signature of COPD exacerbations may be observed in peripheral blood months following the acute illness.,While not predictive in this cross-sectional analysis, these results will be useful in uncovering the molecular pathogenesis of COPD exacerbations.,The online version of this article (doi:10.1186/s12920-014-0072-y) contains supplementary material, which is available to authorized users. | 1 |
Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor.,The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients.,The study included 409 patients from primary care practice in the Netherlands and Switzerland.,We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years.,During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment.,We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis.,Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity.,However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75-0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79-1.00; p = 0.045).,In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time.,Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiety.,Patients with chronic lung disease who stay physically active could reduce their chances of depression and anxiety.,Milo Puhan at the University of Zurich, Switzerland, and co-workers assessed the association between physical activity and the risk of developing various co-existing diseases in 409 patients with chronic obstructive pulmonary disease (COPD).,Co-morbidities such as cardiovascular diseases, diabetes and depression are prevalent in patients with COPD, but the reasons why are not clear.,Puhan’s team assessed patients’ activity levels using an existing questionnaire, and administered another questionnaire to assess mental health.,They followed the cohort for 5 years.,Results indicated weak associations between physical activity levels and most physical illnesses, but there were significant links between higher levels of physical activity and a reduced risk of depression and anxiety.,The results could inform novel COPD treatment programs. | The purpose of this study was to quantify the walking time and frequency of postural changes in daily life in patients with chronic obstructive pulmonary disease (COPD) using a new triaxial accelerometer system.,Twenty-six elderly patients with stable COPD (age 76.8 ± 6.2 years; percent forced expiratory volume in one second [%FEV1] 52.9% ± 26.3%) and 20 age-matched elderly subjects (age 73.0 ± 4.2 years; %FEV1 124.0% ± 22.3%) participated in the study.,The subjects’ time spent walking (slow, fast), standing, sitting, and lying down and the frequency of their postural changes (getting up, standing up) were assessed for 7 consecutive days using an Activity Monitoring And Evaluation System (A-MES™).,We analyzed the relationships among walking times, frequency of postural changes, and physiologic factors in both COPD patients and controls.,The COPD patients’ total walking time, including slow (<2 km/hour) and fast (≥2 km/hour) walking, and their frequency of standing up were significantly lower than those of the age-matched controls (P < 0.01).,The fast walking time in daily life was significantly correlated with the 6-minute walking distance, quadriceps femoris muscle force, and dyspnea (P < 0.01).,These results suggest that both slow (<2 km/hour) and fast (≥2 km/hour) walking time and frequency of postural changes is significantly decreased in COPD patients compared with healthy elderly subjects.,The data also suggest that the COPD patients’ different walking times in daily life are significantly correlated with exercise capacity and dyspnea.,The 6-minute walking distance had the strongest correlation with fast walking time. | 1 |
Exacerbations of asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous.,We sought to investigate the sputum cellular, mediator, and microbiome profiles of both asthma and COPD exacerbations.,Patients with severe asthma or moderate-to-severe COPD were recruited prospectively to a single center.,Sputum mediators were available in 32 asthmatic patients and 73 patients with COPD assessed at exacerbation.,Biologic clusters were determined by using factor and cluster analyses on a panel of sputum mediators.,Patterns of clinical parameters, sputum mediators, and microbiome communities were assessed across the identified clusters.,The asthmatic patients and patients with COPD had different clinical characteristics and inflammatory profiles but similar microbial ecology.,Three exacerbation biologic clusters were identified.,Cluster 1 was COPD predominant, with 27 patients with COPD and 7 asthmatic patients exhibiting increased blood and sputum neutrophil counts, proinflammatory mediators (IL-1β, IL-6, IL-6 receptor, TNF-α, TNF receptors 1 and 2, and vascular endothelial growth factor), and proportions of the bacterial phylum Proteobacteria.,Cluster 2 had 10 asthmatic patients and 17 patients with COPD with increased blood and sputum eosinophil counts, type 2 mediators (IL-5, IL-13, CCL13, CCL17, and CCL26), and proportions of the bacterial phylum Bacteroidetes.,Cluster 3 had 15 asthmatic patients and 29 patients with COPD with increased type 1 mediators (CXCL10, CXCL11, and IFN-γ) and proportions of the phyla Actinobacteria and Firmicutes.,A biologic clustering approach revealed 3 subgroups of asthma and COPD exacerbations, each with different percentages of patients with overlapping asthma and COPD.,The sputum mediator and microbiome profiles were distinct between clusters. | Chronic obstructive pulmonary disease (COPD) is predicted to become the third most common cause of death and the fifth most common cause of disability in the world by 2020.,Recently, variants in the hypoxia-inducible factor 1α (HIF1A), cholinergic receptor, neuronal nicotinic, alpha polypeptide-5, and iron-responsive element-binding protein 2 gene (IREB2) genes were found to be associated with COPD.,This study aims to identify whether the variations in these genes are related to COPD in the Hainan population of the People’s Republic of China.,We genotyped 12 single nucleotide polymorphisms in a case-control study with 200 COPD cases and 401 controls from Hainan, People’s Republic of China.,Odds ratios and 95% confidence intervals were estimated using the chi-squared (χ2) test, genetic model analysis, haplotype analysis, and stratification analysis.,In the genetic model analysis, we found that the genotype T/T of rs13180 of IREB2 decreased the COPD risk by 0.52-fold (P=0.025).,But in the further stratification analysis, we failed to find the association between the selected single nucleotide polymorphisms with COPD risk in Han population.,In addition, the haplotype analysis of HIF1A gene also was not found to be the possible haplotype associated with COPD risk.,Our results support that IREB2 rs13180 is associated with COPD in Hainan population.,And this is the first time the HIF1A polymorphisms in COPD in a Chinese population has been reported, although we failed to find any significant result. | 1 |
Although many hospitals promote self-management to chronic obstructive pulmonary disease (COPD) patients post discharge from hospital, the clinical effectiveness of this is unknown.,We undertook a systematic review of the evidence as part of a Health Technology Assessment review.,A comprehensive search strategy with no language restrictions was conducted across relevant databases from inception to May 2012.,Randomized controlled trials of patients with COPD, recently discharged from hospital after an acute exacerbation and comparing a self-management intervention with control, usual care or other intervention were included.,Study selection, data extraction, and risk of bias assessment were undertaken by two reviewers independently.,Of 13,559 citations, 836 full texts were reviewed with nine randomized controlled trials finally included in quantitative syntheses.,Interventions were heterogeneous.,Five trials assessed highly supported multi-component interventions and four trials were less supported with fewer contacts with health care professionals and mainly home-based interventions.,Total sample size was 1,466 (range 33-464 per trial) with length of follow-up 2-12 months.,Trials varied in quality; poor patient follow-up and poor reporting was common.,No evidence of effect in favor of self-management support was observed for all-cause mortality (pooled hazard ratio =1.07; 95% confidence interval [0.74 to 1.55]; I2=0.0%, [n=5 trials]).,No clear evidence of effect on all-cause hospital admissions was observed (hazard ratio 0.88 [0.61, 1.27] I2=66.0%).,Improvements in St George’s Respiratory Questionnaire score were seen in favor of self-management interventions (mean difference =3.84 [1.29 to 6.40]; I2=14.6%), although patient follow-up rates were low.,There is insufficient evidence to support self-management interventions post-discharge.,There is a need for good quality primary research to identify effective approaches. | Chronic obstructive pulmonary disease (COPD) is characterized by a persistent blockage of airflow, prompting episodes of shortness of breath, commonly leading to hospitalization.,Hospitalization may lead to a decline in physical activity following discharge.,Physical activity has been shown to improve symptoms of COPD and reduce readmissions, and to decrease morbidity and mortality.,This study aims to explore, from the perspectives of people with COPD, the barriers to and enablers of participation in physical activity following hospitalization for COPD.,This study had a qualitative descriptive design and included semistructured interviews with 28 adult COPD patients who had been admitted to hospital with a primary diagnosis of exacerbation of COPD.,A plethora of barriers to but fewer enablers of participation in physical activity and pulmonary rehabilitation were identified for this cohort of people.,The main barriers identified were health-related (comorbidities, COPD symptoms, and physical injury or illness) environment-related (weather, transport, and finance), and self-related.,The main enabling factors reported were access to health professionals and equipment, social support, routine and extracurricular activities, personal goals and motivation, and the effect of physical activity and “feeling better”.,This research provides a snapshot of the barriers to and enablers of physical activity and pulmonary rehabilitation in people with COPD.,It is evident that there are significant barriers which hinder the ability of people with COPD to undertake and continue participation in physical activity and pulmonary rehabilitation.,While there are some enablers that may counter these barriers, it is clear that health professionals dealing with people suffering from COPD need to actively recognize and address barriers to physical activity and pulmonary rehabilitation.,Hospital admission may create an opportunity for implementation of interventions promoting physical activity (such as referral to pulmonary rehabilitation), which may assist in reducing hospital readmission, as well as decreasing morbidity and mortality. | 1 |
There is minimal evidence on the extent to which the occurrence of a severe acute exacerbation of COPD that results in hospitalization affects the subsequent disease course.,Previous studies on this topic did not generate causally-interpretable estimates.,Our aim was to use corrected methodology to update previously reported estimates of the associations between previous and future exacerbations in these patients.,Using administrative health data in British Columbia, Canada (1997-2012), we constructed a cohort of patients with at least one severe exacerbation, defined as an episode of inpatient care with the main diagnosis of COPD based on international classification of diseases (ICD) codes.,We applied a random-effects 'joint frailty' survival model that is particularly developed for the analysis of recurrent events in the presence of competing risk of death and heterogeneity among individuals in their rate of events.,Previous severe exacerbations entered the model as dummy-coded time-dependent covariates, and the model was adjusted for several observable patient and disease characteristics.,35,994 individuals (mean age at baseline 73.7, 49.8% female, average follow-up 3.21 years) contributed 34,271 severe exacerbations during follow-up.,The first event was associated with a hazard ratio (HR) of 1.75 (95%CI 1.69-1.82) for the risk of future severe exacerbations.,This risk decreased to HR = 1.36 (95%CI 1.30-1.42) for the second event and to 1.18 (95%CI 1.12-1.25) for the third event.,The first two severe exacerbations that occurred during follow-up were also significantly associated with increased risk of all-cause mortality.,There was substantial heterogeneity in the individual-specific rate of severe exacerbations.,Even after adjusting for observable characteristics, individuals in the 97.5th percentile of exacerbation rate had 5.6 times higher rate of severe exacerbations than those in the 2.5th percentile.,Using robust statistical methodology that controlled for heterogeneity in exacerbation rates among individuals, we demonstrated potential causal associations among past and future severe exacerbations, albeit the magnitude of association was noticeably lower than previously reported.,The prevention of severe exacerbations has the potential to modify the disease trajectory. | Current treatment strategies to stratify exacerbation risk rely on history of ≥2 events in the previous year.,To understand year-to-year variability and factors associated with consistent exacerbations over time, we present a prospective analysis of the SPIROMICS cohort.,We analyzed SPIROMICS participants with COPD and three years of prospective data (n=1,105).,We classified participants according to yearly exacerbation frequency.,Stepwise logistic regression compared factors associated with individuals experiencing ≥1 AECOPD in every year for three years versus none.,During three years follow-up, 48·7% of participants experienced at least one AECOPD, while the majority (51·3%) experienced none.,Only 2·1% had ≥2 AECOPD in each year.,An inconsistent pattern (both years with and years without AECOPD) was common (41·3% of the group), particularly among GOLD stages 3 and 4 subjects (56·1%).,In logistic regression, consistent AECOPD (≥1 event per year for three years) as compared to no AECOPD were associated with higher baseline symptom burden assessed with the COPD Assessment Test, previous exacerbations, greater evidence of small airway abnormality by computed tomography, lower Interleukin-15 (IL-15) and elevated Interleukin-8 (IL-8).,Although AECOPD are common, the exacerbation status of most individuals varies markedly from year to year.,Among participants who experienced any AECOPD over three years, very few repeatedly experienced ≥2 events/year.,In addition to symptoms and history of exacerbations in the prior year, we identified several novel biomarkers associated with consistent exacerbations, including CT-defined small airway abnormality, IL-15 and IL-8. | 1 |
Oxidative stress is a major driving mechanism in the pathogenesis of COPD.,There is increased oxidative stress in the lungs of COPD patients due to exogenous oxidants in cigarette smoke and air pollution and due to endogenous generation of reactive oxygen species by inflammatory and structural cells in the lung.,Mitochondrial oxidative stress may be particularly important in COPD.,There is also a reduction in antioxidant defences, with inactivation of several antioxidant enzymes and the transcription factors Nrf2 and FOXO that regulate multiple antioxidant genes.,Increased systemic oxidative stress may exacerbate comorbidities and contribute to skeletal muscle weakness.,Oxidative stress amplifies chronic inflammation, stimulates fibrosis and emphysema, causes corticosteroid resistance, accelerates lung aging, causes DNA damage and stimulates formation of autoantibodies.,This suggests that treating oxidative stress by antioxidants or enhancing endogenous antioxidants should be an effective strategy to treat the underlying pathogenetic mechanisms of COPD.,Most clinical studies in COPD have been conducted using glutathione-generating antioxidants such as N-acetylcysteine, carbocysteine and erdosteine, which reduce exacerbations in COPD patients, but it is not certain whether this is due to their antioxidant or mucolytic properties.,Dietary antioxidants have so far not shown to be clinically effective in COPD.,There is a search for more effective antioxidants, which include superoxide dismutase mimetics, NADPH oxidase inhibitors, mitochondria-targeted antioxidants and Nrf2 activators. | Exacerbations constitute a major cause of morbidity and mortality in patients suffering from chronic obstructive pulmonary disease (COPD).,Both bacterial infections, such as those with non-typeable Haemophilus influenzae (NTHi), and exposures to diesel engine emissions are known to contribute to exacerbations in COPD patients.,However, the effect of diesel exhaust (DE) exposure on the epithelial response to microbial stimulation is incompletely understood, and possible differences in the response to DE of epithelial cells from COPD patients and controls have not been studied.,Primary bronchial epithelial cells (PBEC) were obtained from age-matched COPD patients (n = 7) and controls (n = 5).,PBEC were cultured at the air-liquid interface (ALI) to achieve mucociliary differentiation.,ALI-PBECs were apically exposed for 1 h to a stream of freshly generated whole DE or air.,Exposure was followed by 3 h incubation in presence or absence of UV-inactivated NTHi before analysis of epithelial gene expression.,DE alone induced an increase in markers of oxidative stress (HMOX1, 50-100-fold) and of the integrated stress response (CHOP, 1.5-2-fold and GADD34, 1.5-fold) in cells from both COPD patients and controls.,Exposure of COPD cultures to DE followed by NTHi caused an additive increase in GADD34 expression (up to 3-fold).,Importantly, DE caused an inhibition of the NTHi-induced expression of the antimicrobial peptide S100A7, and of the chaperone protein HSP5A/BiP.,Our findings show that DE exposure of differentiated primary airway epithelial cells causes activation of the gene expression of HMOX1 and markers of integrated stress response to a similar extent in cells from COPD donors and controls.,Furthermore, DE further increased the NTHi-induced expression of GADD34, indicating a possible enhancement of the integrated stress response.,DE reduced the NTHi-induced expression of S100A7.,These data suggest that DE exposure may cause adverse health effects in part by decreasing host defense against infection and by modulating stress responses.,The online version of this article (doi:10.1186/s12931-017-0510-4) contains supplementary material, which is available to authorized users. | 1 |
Exercise tests are often used to evaluate the functional status of patients with COPD.,However, to the best of our knowledge, a comprehensive systematic comparison of these tests has not been performed.,We systematically reviewed studies reporting the repeatability and/or reproducibility of these tests, and studies comparing their sensitivity to therapeutic intervention.,A systematic review identified primary manuscripts in English reporting relevant data on the following exercise tests: 6-minute walk test (6MWT) and 12-minute walk test, incremental and endurance shuttle walk tests (ISWT and ESWT, respectively), incremental and endurance cycle ergometer tests, and incremental and endurance treadmill tests.,We identified 71 relevant studies.,Good repeatability (for the 6MWT and ESWT) and reproducibility (for the 6MWT, 12-minute walk test, ISWT, ESWT, and incremental cycle ergometer test) were reported by most studies assessing these tests, providing patients were familiarized with them beforehand.,The 6MWT, ISWT, and particularly the ESWT were reported to be sensitive to therapeutic intervention.,Protocol variations (eg, track layout or supplemental oxygen use) affected performance significantly in several studies.,This review shows that while the validity of several tests has been established, for others further study is required.,Future work will assess the link between these tests, physiological mechanisms, and patient-reported measures. | Chronic Obstructive Pulmonary Disease (COPD) is a worldwide public health concern.,It is also a major source of disability that is often overlooked, depriving patients of effective treatments.,This study describes the development and validation of a questionnaire specifically assessing COPD-related disability.,The DIsability RElated to COPD Tool (DIRECT) was developed according to reference methods, including literature review, patient and clinician interviews and test in a pilot study.,A 12-item questionnaire was included for finalization and validation in an observational cross-sectional study conducted by 60 French pulmonologists, who recruited 275 COPD patients of stage II, III and IV according to the GOLD classification.,Rasch modeling was conducted and psychometric properties were assessed (internal consistency reliability; concurrent and clinical validity).,The DIRECT score was built from the 10 items retained in the Rasch model.,Their internal consistency reliability was excellent (Cronbach’s alpha = 0.95).,The score was highly correlated with the Saint George’s Respiratory Questionnaire Activity score (r = 0.83) and the London Handicap Scale (r = −0.70), a generic disability measure.,It was highly statistically significantly associated to four clinical parameters (P < 0.001): GOLD classification, BODE index, FEV1 and 6-minute walk distance.,DIRECT is a promising tool that could help enhance the management of COPD patients by integrating an evaluation of the COPD-related disability into daily practice. | 1 |
Chronic obstructive pulmonary disease (COPD) is characterized by irreversible, progressive obstruction of lung airflow.,Dyspnea (shortness of breath [SOB]) is the COPD symptom which most negatively impacts patients’ daily activities.,To assess how SOB affects daily activities, 37 items were drafted through focus group discussions and cognitive interviews with COPD patients to develop a patient-reported outcome instrument: the Shortness of Breath with Daily Activities questionnaire (SOBDA).,Psychometric analysis was conducted to reduce the number of items and evaluate the measurement properties of the final SOBDA.,Prospective, observational study of 334 COPD patients, recruited from 24 pulmonology and internal medicine clinics in the United States.,The 37-item SOBDA was administered to patients each evening for 28 days using an electronic diary.,Patients answered every item and rated their level of SOB experienced that day during specific activities.,Item selection was conducted by examining item characteristics, dimensionality, and Rasch model analysis results.,The decision to delete an item was based on psychometric evidence, content validity, and expert clinical input.,The final SOBDA instrument was evaluated for internal consistency, reproducibility, convergent validity, known-groups validity, and responsiveness.,Twenty-four items from the 37-item pool were removed following the item selection process: nine items were removed due to high item-to-item correlations; five due to floor effects; three due to infrequent activity; one due to gender bias; two due to low factor loadings; three due to unordered response options; and one due to expert’s discretion.,Internal consistency and reproducibility of the final SOBDA were demonstrated by Cronbach Alpha = 0.87, and intra-class correlation coefficient = 0.91.,Convergent validity was demonstrated by high correlation with the CRQ-SAS (0.60) and SGRQ-C (0.61).,Known groups validity was demonstrated by significant difference between ratings of the mMRC and clinical global rating of severity.,Evaluation of the ability to detect change was not performed owing to too few responders at the end of the study.,Through the empirical item reduction process, 13 items were selected from the 37-item pool generated during qualitative development.,The final 13-item SOBDA is a reliable and valid instrument for use in clinical trials. | Patient-reported outcome measures (PROMs) are intended to reflect outcomes relevant to patients.,They are increasingly used for healthcare quality improvement.,To produce valid measures, patients should be involved in the development process but it is unclear whether this usually includes people with low literacy skills or learning disabilities.,This potential exclusion raises concerns about whether these groups will be able to use these measures and participate in quality improvement practices.,Taking PROMs for chronic obstructive pulmonary disease (COPD) as an exemplar condition, our review determined the inclusion of people with low literacy skills and learning disabilities in research developing, validating, and using 12 PROMs for COPD patients.,The studies included in our review were based on those identified in two existing systematic reviews and our update of this search.,People with low literacy skills and/or learning disabilities were excluded from the development of PROMs in two ways: explicitly through the participant eligibility criteria and, more commonly, implicitly through recruitment or administration methods that would require high-level reading and cognitive abilities.,None of the studies mentioned efforts to include people with low literacy skills or learning disabilities.,Our findings suggest that people with low literacy skills or learning disabilities are left out of the development of PROMs.,Given that implicit exclusion was most common, researchers and those who administer PROMs may not even be aware of this problem.,Without effort to improve inclusion, unequal quality improvement practices may become embedded in the health system. | 1 |
Twenty per cent of chronic obstructive pulmonary disease (COPD) patients are readmitted for acute exacerbation (AECOPD) within 30 days of discharge.,The prognostic significance of early readmission is not fully understood.,The objective of our study was to estimate the mortality risk associated with readmission for acute exacerbation within 30 days of discharge in COPD patients.,The cohort (n = 378) was divided into patients readmitted (n = 68) and not readmitted (n = 310) within 30 days of discharge.,Clinical, laboratory, microbiological, and severity data were evaluated at admission and during hospital stay, and mortality data were recorded at four time points during follow-up: 30 days, 6 months, 1 year and 3 years.,Patients readmitted within 30 days had poorer lung function, worse dyspnea perception and higher clinical severity.,Two or more prior AECOPD (HR, 2.47; 95% CI, 1.51-4.05) was the only variable independently associated with 30-day readmission.,The mortality risk during the follow-up period showed a progressive increase in patients readmitted within 30 days in comparison to patients not readmitted; moreover, 30-day readmission was an independent risk factor for mortality at 1 year (HR, 2.48; 95% CI, 1.10-5.59).,In patients readmitted within 30 days, the estimated absolute increase in the mortality risk was 4% at 30 days (number needed to harm NNH, 25), 17% at 6-months (NNH, 6), 19% at 1-year (NNH, 6) and 24% at 3 years (NNH, 5).,In conclusion a readmission for AECOPD within 30 days is associated with a progressive increased long-term risk of death. | Exacerbations of chronic obstructive pulmonary disease (COPD) are important events that carry significant consequences for patients.,Some patients experience frequent exacerbations, and are now recognized as a distinct clinical subgroup, the ‘frequent exacerbator’ phenotype.,This is relatively stable over time, occurs across disease severity, and is associated with poorer health outcomes.,These patients are therefore a priority for research and treatment.,The pathophysiology underlying the frequent exacerbator phenotype is complex, with increased airway and systemic inflammation, dynamic lung hyperinflation, changes in lower airway bacterial colonization and a possible increased susceptibility to viral infection.,Frequent exacerbators are also at increased risk from comorbid extrapulmonary diseases including cardiovascular disease, gastroesophageal reflux, depression, osteoporosis and cognitive impairment.,Overall these patients have poorer health status, accelerated forced expiratory volume over 1 s (FEV1) decline, worsened quality of life, and increased hospital admissions and mortality, contributing to increased exacerbation susceptibility and perpetuation of the frequent exacerbator phenotype.,This review article sets out the definition and importance of the frequent exacerbator phenotype, with a detailed examination of its pathophysiology, impact and interaction with other comorbidities.,The online version of this article (doi:10.1186/1741-7015-11-181) contains supplementary material, which is available to authorized users. | 1 |
COPD-6™ is a lung function testing device for a rapid pre-spirometry testing to screen-out at-risk individuals not having COPD and indicating those at risk.,The aim of this study was to validate COPD-6™ lung function testing (index test) in general practice in discriminating patients with COPD out of the population at risk - smokers/ex-smokers with no previous diagnosis of COPD, using measurements at tertiary care as reference standard.,Consecutive 227 subjects (115 women, 185 smokers/42 ex-smokers, ≥20 pack-years) with no previous diagnosis of COPD, aged 52.5 (SD 6.8) years from 26 general practitioners (GPs) were recruited, lung function tested with COPD-6™, referred to the tertiary institution for repeated COPD-6™ testing followed by spirometry with a bronchodilator (salbutamol), examination, and pulmonologist consultation for the diagnosis and severity of COPD.,COPD was diagnosed in 43 subjects (18.9 %), with an AUC of 0.827 (95 % CI 0.769-0.875, P < 0.001) for the diagnosis of COPD when lung function was measured using COPD-6™ in GP’s office with a specificity of 100 % (95 % CI, 97.95-100 %) but a very low sensitivity of 32.56 % (95 % CI, 20.49-47.48 %).,Significant agreement for forced expiratory volume in 1 s measured at GP’s office and at lung function lab was found (mean difference 0.01 L, p = 0.667) but not for other measured parameters (p < 0.001 for all).,Our study results point out that active case finding in a population at risk for COPD should be instituted (almost 20 % of undiagnosed COPD).,Based on our results lung function testing with COPD-6™ can substitute spirometry testing in cases where it is not readily available to the patient/physician taken into account that the traditional FEV1/FEV6 cutoff value of <0.7 is not the only criterion for diagnosis and/or further referral.,ClinicalTrials.gov Identifier NCT01550679 Registered 28 September 2014, retrospectively registered | COPD has a profound impact on daily life, yet remains underdiagnosed and undertreated.,We set out to develop a brief, reliable, self-scored questionnaire to identify individuals likely to have COPD.,COPD-PS™ development began with a list of concepts identified for inclusion using expert opinion from a clinician working group comprised of pulmonologists (n = 5) and primary care clinicians (n = 5).,A national survey of 697 patients was conducted at 12 practitioner sites.,Logistic regression identified items discriminating between patients with and without fixed airflow obstruction (AO, postbronchodilator FEV1/FVC < 70%).,ROC analyses evaluated screening accuracy, compared scoring options, and assessed concurrent validity.,Convergent and discriminant validity were assessed via COPD-PS and SF-12v2 score correlations.,For known-groups validation, COPD-PS differences between clinical groups were tested.,Test-retest reliability was evaluated in a 20% sample.,Of 697 patients surveyed, 295 patients met expert review criteria for spirometry performance; 38% of these (n = 113) had results indicating AO.,Five items positively predicted AO (p < 0.0001): breathlessness, productive cough, activity limitation, smoking history, and age.,COPD-PS scores accurately classified AO status (area under ROC curve = 0.81) and reliable (r = 0.91).,Patients with spirometry indicative of AO scored significantly higher (6.8, SD = 1.9; p < 0.0001) than patients without AO (4.0, SD = 2.3).,Higher scores were associated with more severe AO, bronchodilator use, and overnight hospitalization for breathing problems.,With the prevalence of COPD in the studied cohort, a score on the COPD-PS of greater than five was associated with a positive predictive value of 56.8% and negative predictive value of 86.4%.,The COPD-PS accurately classified physician-reported COPD (AUC = 0.89).,The COPD-PS is a brief, accurate questionnaire that can identify individuals likely to have COPD. | 1 |
Chronic obstructive pulmonary disease (COPD) patients present a high prevalence of cardiovascular disease.,This excess of comorbidity could be related to a common pathogenic mechanism, but it could also be explained by the existence of common risk factors.,The objective of this study was to determine whether COPD patients present greater cardiovascular comorbidity than control subjects and whether COPD can be considered a risk factor per se.,1200 COPD patients and 300 control subjects were recruited for this multicenter, cross-sectional, case-control study.,Compared with the control group, the COPD group showed a significantly higher prevalence of ischemic heart disease (12.5% versus 4.7%; P < 0.0001), cerebrovascular disease (10% versus 2%; P < 0.0001), and peripheral vascular disease (16.4% versus 4.1%; P < 0.001).,In the univariate risk analysis, COPD, hypertension, diabetes, obesity, and dyslipidemia were risk factors for ischemic heart disease.,In the multivariate analysis adjusted for the remaining factors, COPD was still an independent risk factor (odds ratio: 2.23; 95% confidence interval: 1.18-4.24; P = 0.014).,COPD patients show a high prevalence of cardiovascular disease, higher than expected given their age and the coexistence of classic cardiovascular risk factors. | We examined the influence of overweight and obesity on pulmonary function, exercise tolerance, quality of life and response to pulmonary rehabilitation in COPD.,261 patients with COPD were divided into three groups: normal body mass index (BMI), overweight and obese.,Baseline and post rehabilitation pulmonary function, 6-min walking test (6MWT), endurance time during a constant workrate exercise test (CET) and St.,George's Respiratory Questionnaire (SGRQ) scores were compared between all three classes of BMI.,At baseline, obese and overweight patients had less severe airflow obstruction compared to normal BMI patients.,There was no baseline difference in CET performance or SGRQ scores across BMI classes and 6MWT was reduced in the presence of obesity (p < 0.01).,Compared to baseline, post-rehabilitation 6MWT, CET performance and SGRQ scores improved significantly in each group (p < 0.01), but 6MWT was still significantly lower in the presence of obesity.,Walking, but not cycling performance was worse in obese patients.,This difference was maintained post rehabilitation despite significant improvements.,Weight excess may counterbalance the effect of a better preserved respiratory function in the performance of daily activities such as walking.,However, obesity and overweight did not influence the magnitude of improvement after pulmonary rehabilitation. | 1 |
Self-management interventions (SMIs) are recommended for individuals with COPD to help monitor symptoms and optimize health-related quality of life (HRQOL).,However, SMIs vary widely in content, delivery, and intensity, making it unclear which methods and techniques are associated with improved outcomes.,This systematic review aimed to summarize the current evidence base surrounding the effectiveness of SMIs for improving HRQOL in people with COPD.,Systematic reviews that focused upon SMIs were eligible for inclusion.,Intervention descriptions were coded for behavior change techniques (BCTs) that targeted self-management behaviors to address 1) symptoms, 2) physical activity, and 3) mental health.,Meta-analyses and meta-regression were used to explore the association between health behaviors targeted by SMIs, the BCTs used, patient illness severity, and modes of delivery, with the impact on HRQOL and emergency department (ED) visits.,Data related to SMI content were extracted from 26 randomized controlled trials identified from 11 systematic reviews.,Patients receiving SMIs reported improved HRQOL (standardized mean difference =−0.16; 95% confidence interval [CI] =−0.25, −0.07; P=0.001) and made fewer ED visits (standardized mean difference =−0.13; 95% CI =−0.23, −0.03; P=0.02) compared to patients who received usual care.,Patients receiving SMIs targeting mental health alongside symptom management had greater improvement of HRQOL (Q=4.37; P=0.04) and fewer ED visits (Q=5.95; P=0.02) than patients receiving SMIs focused on symptom management alone.,Within-group analyses showed that HRQOL was significantly improved in 1) studies with COPD patients with severe symptoms, 2) single-practitioner based SMIs but not SMIs delivered by a multidisciplinary team, 3) SMIs with multiple sessions but not single session SMIs, and 4) both individual- and group-based SMIs.,SMIs can be effective at improving HRQOL and reducing ED visits, with those targeting mental health being significantly more effective than those targeting symptom management alone. | The global burden of chronic obstructive pulmonary disease (COPD) continues to grow in part due to better outcomes in other major diseases and in part because a substantial portion of the worldwide population continues to be exposed to inhalant toxins.,However, a disproportionate burden of COPD occurs in people of low socioeconomic status (SES) due to differences in health behaviors, sociopolitical factors, and social and structural environmental exposures.,Tobacco use, occupations with exposure to inhalant toxins, and indoor biomass fuel (BF) exposure are more common in low SES populations.,Not only does SES affect the risk of developing COPD and etiologies, it is also associated with worsened COPD health outcomes.,Effective interventions in these people are needed to decrease these disparities.,Efforts that may help lessen these health inequities in low SES include 1) better surveillance targeting diagnosed and undiagnosed COPD in disadvantaged people, 2) educating the public and those involved in health care provision about the disease, 3) improving access to cost-effective and affordable health care, and 4) markedly increasing the efforts to prevent disease through smoking cessation, minimizing use and exposure to BF, and decreasing occupational exposures.,COPD is considered to be one the most preventable major causes of death from a chronic disease in the world; therefore, effective interventions could have a major impact on reducing the global burden of the disease, especially in socioeconomically disadvantaged populations. | 1 |
Exercise tolerance decreases as COPD progresses.,Pulmonary hypertension (PH) is common in COPD and may reduce performance further.,COPD patients with and without PH could potentially be identified by cardiopulmonary exercise test (CPET).,However, results from previous studies are diverging, and a unified conclusion is missing.,We hypothesized that CPET combined with arterial blood gases is useful to discriminate between COPD outpatients with and without PH.,In total, 93 COPD patients were prospectively included.,Pulmonary function tests, right heart catheterization, and CPET with blood gases were performed.,The patients were divided, by mean pulmonary artery pressure, into COPD-noPH (<25 mmHg) and COPD-PH (≥25 mmHg) groups.,Linear mixed models (LMMs) were fitted to estimate differences when repeated measurements during the course of exercise were considered and adjusted for gender, age, and airway obstruction.,Ventilatory and/or hypoxemic limitation was the dominant cause of exercise termination.,In LMM analyses, significant differences between COPD-noPH and COPD-PH were observed for PaO2, SaO2, PaCO2, ventilation, respiratory frequency, and heart rate.,PaO2 <61 mmHg (8.1 kPa) during unloaded pedaling, the only load level achieved by all the patients, predicted PH with a sensitivity of 86% and a specificity of 78%.,During CPET, low exercise performance and PaO2 strongly indicated PH in COPD patients. | Exertional dyspnea scales (EDS) and health-related quality-of-life questionnaires (HRQoLQs) are used to assess chronic obstructive pulmonary disease (COPD).,The GOLD guidelines categorize patients according to either 1 of these 2 domains, the lung function and the frequency of acute exacerbations in the preceding year, however with inconsistent results.,Combining EDS and HRQoLQs may yield better results; however, the best combination is unclear.,Whether the EDS quantifies the exercise capacity or the dyspnea perception is also unclear.,The study was designed to correlate the EDS with exercise capacity and dyspnea perception and to evaluate the best combination of the EDS and HRQoLQ.,Three EDS were compared by exercise capacity and Borg scores at rest and during exercise in 57 patients with COPD.,Three HRQoLQs were compared by 4 domains of clinical assessments, and 2 types of exercise.,The strength of correlation |r| was categorized by quartiles from <0.3 to ≥0.6.,The EDS was better correlated with exercise capacities (|r| = 0.29-0.65, P < 0.05-<0.0001) than with the resting and exertional Borg scores (|r| = 0.08-0.55, P = NS- <0.0001).,The EDS were moderately to strongly interrelated, but this correlation was weaker when including Oxygen-cost Diagram (OCD) (with the modified Medical Research Council, mMRC r = −0.56, with the baseline dyspnea index, BDI r = 0.49 vs. mMRC with BDI r = −0.73); however, the OCD had the strongest correlation with walking distance (r = 0.65, vs mMRC r = −0.59, BDI r = 0.5) and peak oxygen uptake (r = 0.39 vs mMRC r = −0.29, BDI r = 0.36).,Among the HRQoLQs, the COPD assessment test (CAT) was most strongly correlated with the St.,George Respiratory Questionnaire (SGRQ) (r = 0.77) and similar to the SGRQ regarding significant correlations with the other instruments (|r| = 0.29-0.67 vs.,0.36-0.77) but poorly with walking distance (r = −0.02).,The OCD was mildly correlated with the CAT (r = −0.4).,The EDS was more related to the exercise capacity than to the dyspnea perception and the CAT was most closely related to the other instruments but poorly with walking distance.,The OCD can be used to compensate for this weak correlation.,The study suggests using the CAT and the OCD simultaneously when undertaking clinical evaluation of patients with COPD. | 1 |
Utilizing data from the Continuing to Confront COPD (chronic obstructive pulmonary disease) International Physician Survey, this study aimed to describe physicians’ knowledge and application of the GOLD (Global initiative for chronic Obstructive Lung Disease) Global Strategy for the Diagnosis, Management and Prevention of COPD diagnosis and treatment recommendations and compare performance between primary care physicians (PCPs) and respiratory specialists.,Physicians from 12 countries were sampled from in-country professional databases; 1,307 physicians (PCP to respiratory specialist ratio three to one) who regularly consult with COPD, emphysema, or chronic bronchitis patients were interviewed online, by telephone or face to face.,Physicians were questioned about COPD risk factors, prognosis, diagnosis, and treatment, including knowledge and application of the GOLD global strategy using patient scenarios.,Physicians reported using spirometry routinely (PCPs 82%, respiratory specialists 100%; P<0.001) to diagnose COPD and frequently included validated patient-reported outcome measures (PCPs 67%, respiratory specialists 81%; P<0.001).,Respiratory specialists were more likely than PCPs to report awareness of the GOLD global strategy (93% versus 58%, P<0.001); however, when presented with patient scenarios, they did not always perform better than PCPs with regard to recommending GOLD-concordant treatment options.,The proportion of PCPs and respiratory specialists providing first- or second-choice treatment options concordant with GOLD strategy for a GOLD B-type patient was 38% versus 67%, respectively.,For GOLD C and D-type patients, the concordant proportions for PCPs and respiratory specialists were 40% versus 38%, and 57% versus 58%, respectively.,This survey of physicians in 12 countries practicing in the primary care and respiratory specialty settings showed high awareness of COPD-management guidelines.,Frequent use of guideline-recommended COPD diagnostic practices was reported; however, gaps in the application of COPD-treatment recommendations were observed, warranting further evaluation to understand potential barriers to adopt guideline recommendations. | Chronic obstructive pulmonary disease (COPD) is a multicomponent disorder that leads to substantial disability, impaired quality of life, and increased mortality.,Although the majority of COPD patients are first diagnosed and treated in primary care practices, there is comparatively little information on the management of COPD patients in primary care.,A web-based pilot survey was conducted to evaluate the primary care physician’s, or general practitioner’s (GP’s), knowledge, understanding, and management of COPD in twelve territories across the Asia-Pacific region, Africa, eastern Europe, and Latin America, using a 10-minute questionnaire comprising 20 questions and translated into the native language of each participating territory.,The questionnaire was administered to a total of 600 GPs (50 from each territory) involved in the management of COPD patients and all data were collated and analyzed by an independent health care research consultant.,This survey demonstrated that the GPs’ understanding of COPD was variable across the territories, with large numbers of GPs having very limited knowledge of COPD and its management.,A consistent finding across all territories was the underutilization of spirometry (median 26%; range 10%-48%) and reliance on X-rays (median 14%; range 5%-22%) for COPD diagnosis, whereas overuse of blood tests (unspecified) was particularly high in Russia and South Africa.,Similarly, there was considerable underrecognition of the importance of exacerbation history as an important factor of COPD and its initial management in most territories (median 4%; range 0%-22%).,Management of COPD was well below guideline-recommended levels in most of the regions investigated.,The findings of this survey suggest there is a need for more ongoing education and information, specifically directed towards GPs outside of Europe and North America, and that global COPD guidelines appear to have limited reach and application in most of the areas studied. | 1 |
To examine the relationship between gastroesophageal reflux (GER) and COPD exacerbations.,We conducted a systematic search of various electronic databases for articles published up through December of 2012.,Studies considered eligible for inclusion were those dealing with COPD, COPD exacerbations, and GER; comparing at least two groups (COPD vs. controls or GER vs. controls); and describing relative risks (RRs) and prevalence ratios-or ORs and their respective 95% CIs (or presenting enough data to allow further calculations) for the association between GER and COPD-as well as exacerbation rates.,Using a standardized form, we extracted data related to the study design; criteria for GER diagnosis; age, gender, and number of participants; randomization method; severity scores; methods of evaluating GER symptoms; criteria for defining exacerbations; exacerbation rates (hospitalizations, ER visits, unscheduled clinic visits, prednisone use, and antibiotic use); GER symptoms in COPD group vs. controls; mean number of COPD exacerbations (with symptoms vs. without symptoms); annual frequency of exacerbations; GER treatment; and severity of airflow obstruction.,Overall, GER was clearly identified as a risk factor for COPD exacerbations (RR = 7.57; 95% CI: 3.84-14.94), with an increased mean number of exacerbations per year (mean difference: 0.79; 95% CI: 0.22-1.36).,The prevalence of GER was significantly higher in patients with COPD than in those without (RR = 13.06; 95% CI: 3.64-46.87; p < 0.001).,GER is a risk factor for COPD exacerbations.,The role of GER in COPD management should be studied in greater detail. | Antibiotic overuse in respiratory illness is common and is associated with drug resistance and hospital-acquired infection.,Biomarkers that can identify bacterial infections may reduce antibiotic prescription.,We aimed to compare the usefulness of the biomarkers procalcitonin and C-reactive protein (CRP) in patients with pneumonia or exacerbations of asthma or COPD.,Patients with a diagnosis of community-acquired pneumonia or exacerbation of asthma or COPD were recruited during the winter months of 2006 to 2008.,Demographics, clinical data, and blood samples were collected.,Procalcitonin and CRP concentrations were measured from available sera.,Sixty-two patients with pneumonia, 96 with asthma, and 161 with COPD were studied.,Serum procalcitonin and CRP concentrations were strongly correlated (Spearman rank correlation coefficient [rs] = 0.56, P < .001).,Patients with pneumonia had increased procalcitonin and CRP levels (median [interquartile range] 1.27 ng/mL [2.36], 191 mg/L [159]) compared with those with asthma (0.03 ng/mL [0.04], 9 mg/L [21]) and COPD (0.05 ng/mL [0.06], 16 mg/L [34]).,The area under the receiver operating characteristic curve (95% CI) for distinguishing between patients with pneumonia (antibiotics required) and exacerbations of asthma (antibiotics not required), for procalcitonin and CRP was 0.93 (0.88-0.98) and 0.96 (0.93-1.00).,A CRP value > 48 mg/L had a sensitivity of 91% (95% CI, 80%-97%) and specificity of 93% (95% CI, 86%-98%) for identifying patients with pneumonia.,Procalcitonin and CRP levels can both independently distinguish pneumonia from exacerbations of asthma.,CRP levels could be used to guide antibiotic therapy and reduce antibiotic overuse in hospitalized patients with acute respiratory illness. | 1 |
Patients with chronic obstructive pulmonary disease (COPD) experience respiratory symptoms, which impair quality of life.,This pooled analysis of two Phase III studies assessed the impact of aclidinium/formoterol on patients with COPD categorized by symptom status.,Data were pooled from two 24-week, randomized, placebo-controlled studies of twice-daily aclidinium/formoterol 400/12 µg in moderate-to-severe COPD (ACLIFORM [NCT01462942] and AUGMENT [NCT01437397]).,These post hoc analyses evaluated the efficacy of aclidinium/formoterol versus placebo or monotherapies in patients defined as less/more symptomatic by a) Evaluating Respiratory Symptoms (E-RS™) score ≥10/<10 and b) Baseline Dyspnea Index score <7/≥7.,Endpoints included trough and 1-hour morning postdose forced expiratory volume in 1 second (FEV1), Transition Dyspnea Index, E-RS total score, early-morning and nighttime symptom severity, early-morning limitation of activities, and exacerbation rate.,Data for 3,394 patients were analyzed (mean age: 63.5 years; 60.5% male).,In both definitions of less and more symptomatic patients, aclidinium/formoterol improved 1-hour morning postdose FEV1 from baseline at week 24 versus placebo (P<0.001) and both monotherapies (P<0.05).,Aclidinium/formoterol improved trough FEV1 from baseline in both groups versus placebo (P<0.05) and formoterol (P<0.05); improvements were greater in more symptomatic patients.,Improvements versus aclidinium were also observed in more symptomatic patients (P<0.05).,Aclidinium/formoterol improved dyspnea, early-morning symptom severity, and limitation of activities versus placebo in both less and more symptomatic patients (P<0.001).,In more symptomatic patients, aclidinium/formoterol also improved E-RS total score and severity of nighttime symptoms from baseline versus placebo and one or both monotherapies (P<0.05).,The rate of moderate/severe exacerbations was reduced with aclidinium/formoterol versus placebo in more symptomatic patients.,Aclidinium/formoterol 400/12 µg provided consistent improvements in bronchodilation and symptoms versus monotherapies and reduced exacerbations versus placebo in more symptomatic patients with moderate-to-severe COPD, regardless of the definition used.,Furthermore, patients with a low symptom burden achieved benefits with aclidinium/formoterol versus monotherapies in postdose FEV1, dyspnea, and early-morning symptoms. | Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | 1 |
Blood biomarkers are increasingly used to stratify high risk chronic obstructive pulmonary disease (COPD) patients; however, there are fewer studies that have investigated multiple biomarkers and replicated in multiple large well-characterized cohorts of susceptible current and former smokers.,We used two MSD multiplex panels to measure 9 cytokines and chemokines in 2123 subjects from COPDGene and 1117 subjects from SPIROMICS.,These biomarkers included: interleukin (IL)-2, IL-6, IL-8, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, eotaxin/CCL-11, eotaxin-3/CCL-26, and thymus and activation-regulated chemokine (TARC)/CCL-17.,Regression models adjusted for clinical covariates were used to determine which biomarkers were associated with the following COPD phenotypes: airflow obstruction (forced expiratory flow at 1 s (FEV1%) and FEV1/forced vital capacity (FEV1/FVC), chronic bronchitis, COPD exacerbations, and emphysema.,Biomarker-genotype associations were assessed by genome-wide association of single nucleotide polymorphisms (SNPs).,Eotaxin and IL-6 were strongly associated with airflow obstruction and accounted for 3-5% of the measurement variance on top of clinical variables.,IL-6 was associated with progressive airflow obstruction over 5 years and both IL-6 and IL-8 were associated with progressive emphysema over 5 years.,None of the biomarkers were consistently associated with chronic bronchitis or COPD exacerbations.,We identified one novel SNP (rs9302690 SNP) that was associated with CCL17 plasma measurements.,When assessing smoking related pulmonary disease, biomarkers of inflammation such as IL-2, IL-6, IL-8, and eotaxin may add additional modest predictive value on top of clinical variables alone.,COPDGene (ClinicalTrials.gov Identifier: NCT02445183).,Subpopulations and Intermediate Outcomes Measures in COPD Study (SPIROMICS) (ClinicalTrials.gov Identifier: NCT 01969344).,The online version of this article (10.1186/s12931-017-0662-2) contains supplementary material, which is available to authorized users. | In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation.,However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown.,To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers.,Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry.,IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA.,In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers.,IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers.,In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups.,The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects.,The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers.,IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups.,Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD. | 1 |
Concerns have been raised that treatment of COPD with inhaled corticosteroids may increase pneumonia risk.,Responding to a request from the European Medicines Agency Pharmacovigilance Risk Assessment Committee, a pooled analysis of interventional studies compared pneumonia risk with inhaled budesonide-containing versus non-budesonide-containing treatments and the impact of other clinically relevant factors.,AstraZeneca-sponsored, parallel-group, double-blind, randomized controlled trials meeting the following criteria were included: >8 weeks’ duration; ≥60 patients with COPD; inhaled budesonide treatment arm (budesonide/formoterol or budesonide); and non-budesonide-containing comparator arm (formoterol or placebo).,Primary and secondary outcomes were time to first pneumonia treatment-emergent serious adverse event (TESAE) and treatment-emergent adverse event (TEAEs), respectively, analyzed using Cox regression models stratified by study.,Eleven studies were identified; 10,570 out of 10,574 randomized patients receiving ≥1 dose of study treatment were included for safety analysis (budesonide-containing, n=5,750; non-budesonide-containing, n=4,820).,Maximum exposure to treatment was 48 months.,The overall pooled hazard ratio (HR), comparing budesonide versus non-budesonide-containing treatments, was 1.15 for pneumonia TESAEs (95% confidence interval [CI]: 0.83, 1.57) and 1.13 for pneumonia TEAEs (95% CI: 0.94, 1.36).,The annual incidence of pneumonia TESAEs was 1.9% and 1.5% for budesonide-containing and non-budesonide-containing treatments, respectively.,Comparing budesonide/formoterol with non-budesonide-containing treatment, the HRs for pneumonia TESAEs and TEAEs were 1.00 (95% CI: 0.69, 1.44) and 1.21 (95% CI: 0.93, 1.57), respectively.,For budesonide versus placebo, HRs were 1.57 for pneumonia TESAEs (95% CI: 0.90, 2.74) and 1.07 for pneumonia TEAEs (95% CI: 0.83, 1.38).,This pooled analysis found no statistically significant increase in overall risk for pneumonia TESAEs or TEAEs with budesonide-containing versus non-budesonide-containing treatments.,However, a small increase in risk with budesonide-containing treatment cannot be ruled out; there is considerable heterogeneity in study designs and patient characteristics, particularly in the early budesonide studies, and each study contributes <40 pneumonia TESAEs. | Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular morbidity and mortality.,Elevated arterial stiffness, measured by aortic pulse wave velocity (aPWV), is a cardiovascular risk surrogate and is potentially modifiable by inhaled corticosteroid/long-acting beta2-agonist combinations in patients with COPD.,The effects of once-daily inhaled fluticasone furoate/vilanterol (FF/VI) 100/25 µg, VI 25 µg, versus placebo on arterial stiffness in patients with COPD and baseline aPWV ≥11.0 m/s were investigated in a 24-week, multicenter, double-blind, randomized, stratified (by COPD exacerbation history), parallel-group, placebo-controlled trial.,Eligible patients were ≥40 years old, with ≥10 pack-year smoking history, forced expiratory volume in 1 s (FEV1)/forced vital capacity ≤0.70, and post-bronchodilator FEV1 ≤70% of predicted.,Patients with a major cardiovascular event in the previous 6 months/current severe heart failure/uncontrolled hypertension were excluded.,Primary endpoint is change from baseline in aPWV after 24 weeks of treatment.,Safety analyses included adverse events (AEs).,The intent-to-treat population included 430 patients: FF/VI (n=135), VI (n=154), and placebo (n=141).,Patients were predominantly male (79%) and Asian or White (each 48%), with a mean age of 68.5 years (standard deviation [SD] =7.9), percentage predicted post-bronchodilator FEV1 50.1% (SD =13.3), and aPWV 13.26 m/s (SD =2.22) at screening.,At 24 weeks, mean (standard error [SE]) changes from baseline in aPWV were −1.75 m/s (SE =0.26, FF/VI), −1.95 m/s (SE =0.24, VI), and −1.97 m/s (SE =0.28, placebo).,AEs occurred in 57% (FF/VI), 51% (VI), and 41% (placebo) of patients.,No differences were observed in aPWV-adjusted mean change from baseline for FF/VI 100/25 µg, compared with placebo. | 1 |
We recently reported that current smokers and those with COPD had higher airway epithelial cell expression of the angiotensin-converting enzyme II (ACE-2) viral entry receptor [1].,We thus read with great interest the work of P.,Russo and co-workers, which proposes a mechanism for this finding, namely that this upregulation is mediated by nicotine exposure specifically through the α7 subtype of nicotine acetylcholine receptors (α7-nAChR).,While exposure to increasing concentrations of nicotine caused epithelial cells to increase ACE-2 levels, subsequent gene silencing of α7-nAChR appeared to significantly dampen this response.,A secondary transcriptome sequencing analysis of our cohort (consisting of 42 subjects who underwent bronchoscopy for epithelial cell brushings [1]) reveals evidence in support of this hypothesis.,α7-nAChR may upregulate ACE-2https://bit.ly/2xS0cfT | Exacerbations affect morbidity in chronic obstructive pulmonary disease (COPD).,We sought to evaluate the association between exacerbation frequency and spirometric and health status changes over time using data from a large, long-term trial.,This retrospective analysis of data from the 4-year UPLIFT® (Understanding Potential Long-term Impacts on Function with Tiotropium) trial compared tiotropium with placebo.,Annualized rates of decline and estimated mean differences at each time point were analyzed using a mixed-effects model according to subgroups based on exacerbation frequency (events per patient-year: 0, >0-1, >1-2, and >2).,Spirometry and the St George’s Respiratory Questionnaire (SGRQ) were performed at baseline and every 6 months (also at one month for spirometry).,In total, 5992 patients (mean age 65 years, 75% male) were randomized.,Higher exacerbation frequency was associated with lower baseline postbronchodilator forced expiratory volume in one second (FEV1) (1.40, 1.36, 1.26, and 1.14 L) and worsening SGRQ scores (43.7, 44.1, 47.8, and 52.4 units).,Corresponding rates of decline in postbronchodilator FEV1 (mL/year) were 40, 41, 43, and 48 (control), and 34, 38, 48, and 49 (tiotropium).,Values for postbronchodilator forced vital capacity decline (mL/year) were 45, 56, 74, and 83 (control), and 43, 57, 83, and 95 (tiotropium).,The rates of worsening in total SGRQ score (units/year) were 0.72, 1.16, 1.44, and 1.99 (control), and 0.38, 1.29, 1.68, and 2.86 (tiotropium).,The proportion of patients who died (intention-to-treat analysis until four years [1440 days]) for the entire cohort increased with increasing frequency of hospitalized exacerbations.,Increasing frequency of exacerbations worsens the rate of decline in lung function and health-related quality of life in patients with COPD.,Increasing rates of hospitalized exacerbations are associated with increasing risk of death. | 1 |
Some patients with chronic obstructive pulmonary disease (COPD) show increased airway inflammation and bacterial colonization during stable phase.,The aim of this study was to follow COPD patients and investigate chronic colonization with pathogenic bacteria during stable disease phase, and relate these findings to clinical parameters, inflammatory pattern, lung function, and exacerbations.,Forty-three patients with COPD were included while in a stable state and followed up monthly until exacerbation or for a maximum of 6 months.,The patients completed the Clinical COPD Questionnaire and Medical Research Council dyspnea scale questionnaires, and exhaled breath condensate was collected, followed by spirometry, impulse oscillometry, and sputum induction.,Ten patients were chronically colonized (ie, colonized at all visits) with Haemophilus influenzae during stable phase.,These patients had higher sputum levels of leukotriene B4 (P<0.001), 8-isoprostane (P=0.002), myeloperoxidase activity (P=0.028), and interleukin-8 (P=0.02) during stable phase when compared with other patients.,In addition, they had lower forced vital capacity (P=0.035) and reactance at 5 Hz (P=0.034), but there was no difference in forced expiratory volume in 1 second (FEV1), FEV1 % predicted, forced vital capacity % predicted, exhaled breath condensate biomarkers, C-reactive protein, or Clinical COPD Questionnaire and Medical Research Council dyspnea scale results.,Three patients had intermittent colonization (colonized at only some visits) of H. influenzae during stable phase, and had lower levels of inflammatory biomarkers in sputum when compared with the chronically colonized patients.,The difference in airway inflammation seen during stable phase in patients chronically colonized with H. influenzae was not observed during exacerbations.,Some COPD patients who were chronically colonized with H. influenzae during stable phase showed increased airway inflammation and reduced lung volumes when compared with non-chronically colonized patients. | Bacterial infection of the lower respiratory tract in chronic obstructive pulmonary disease (COPD) patients is common both in stable patients and during acute exacerbations.,The most frequent bacteria detected in COPD patients is Haemophilus influenzae, and it appears this organism is uniquely adapted to exploit immune deficiencies associated with COPD and to establish persistent infection in the lower respiratory tract.,The presence of bacteria in the lower respiratory tract in stable COPD is termed colonization; however, there is increasing evidence that this is not an innocuous phenomenon but is associated with airway inflammation, increased symptoms, and increased risk for exacerbations.,In this review, we discuss host immunity that offers protection against H. influenzae and how disturbance of these mechanisms, combined with pathogen mechanisms of immune evasion, promote persistence of H. influenzae in the lower airways in COPD.,In addition, we examine the role of H. influenzae in COPD exacerbations, as well as interactions between H. influenzae and respiratory virus infections, and review the role of treatments and their effect on COPD outcomes.,This review focuses predominantly on data derived from human studies but will refer to animal studies where they contribute to understanding the disease in humans. | 1 |
The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999-2000.,Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples.,Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments.,Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis.,The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale.,Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey.,COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%-9%.,In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%-14%) than among women (range 5%-11%).,A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries.,Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment.,This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey.,A significant burden of COPD was demonstrated by symptoms and health care-resource use, similar to that reported in the original survey. | To evaluate the influence of heart disease on clinical characteristics, quality of life, use of health resources, and costs of patients with COPD followed at primary care settings under common clinical practice conditions.,Epidemiologic, observational, and descriptive study (EPIDEPOC study).,Patients ≥ 40 years of age with stable COPD attending primary care settings were included.,Demographic, clinical characteristics, quality of life (SF-12), seriousness of the disease, and treatment data were collected.,Results were compared between patients with or without associated heart disease.,A total of 9,390 patients with COPD were examined of whom 1,770 (18.8%) had heart disease and 78% were males.,When comparing both patient groups, significant differences were found in the socio-demographic characteristics, health profile, comorbidities, and severity of the airway obstruction, which was greater in patients with heart disease.,Differences were also found in both components of quality of life, physical and mental, with lower scores among those patients with heart disease.,Higher frequency of primary care and pneumologist visits, emergency-room visits and number of hospital admissions were observed among patients with heart diseases.,The annual total cost per patient was significantly higher in patients with heart disease; 2,937 ± 2,957 vs. 1,749 ± 2,120, p < 0.05.,Variables that were showed to be independently associated to COPD in subjects with hearth conditions were age, being inactive, ex-smokers, moderate physical exercise, body mass index, concomitant blood hypertension, diabetes, anxiety, the SF-12 physical and mental components and per patient per year total cost.,Patients with COPD plus heart disease had greater disease severity and worse quality of life, used more healthcare resources and were associated with greater costs compared to COPD patients without known hearth disease. | 1 |
Bronchodilators administered through inhalation devices are the mainstay treatment for patients with obstructive lung diseases.,Patients do not view devices as interchangeable.,This systematic review and meta-analysis examined device feature preferences among patients with obstructive lung diseases treated with handheld inhalers.,PubMed, EMBASE, PsycINFO, Cochrane, and Google Scholar were searched to identify publications between 2010 and 2019 that met the following criteria:,English language;,studied adults with chronic obstructive pulmonary disease, bronchitis, or emphysema; and,reported patients’ device feature preferences specific to metered-dose inhalers, dry powder inhalers, and soft mist inhalers.,A manual search extended the study period from 2001 to 2019.,Random-effects models were used to generate pooled mean effect sizes and 95% confidence intervals (CIs) for preferred device features.,Heterogeneity was measured by the I2 statistic.,Nineteen studies (n = 11,256) were included in this meta-analysis.,Average age ranged from 50.4 to 74.3 years.,The majority of patients were male (57%) and had chronic obstructive pulmonary disease (92%).,Patients preferred the following device features:,small size (71.7%, 95% CI: 46.3, 97.1; n = 604, 3 studies);,rapid medication administration (64.9%, 95% CI: 36.5, 93.4; n = 745, 3 studies);,durability (62.1%, 95% CI: 39.7, 84.4; n = 4,500, 4 studies);,a dose counter (52.3%, 95% CI: 20.7, 83.9; n = 4,536, 4 studies);,portability (51.8%, 95% CI: 29.1, 74.5; n = 4,975, 7 studies);,perceived ease of use (51.2%, 95% CI: 35.6, 66.7; n = 5,878, 10 studies); and,perceived ease of dose preparation (50.1%, 95% CI: 26.2, 73.9; n = 4,003, 4 studies).,Adults with obstructive lung diseases preferred small inhaler devices that were portable, durable, perceived as easy to use, and fast in medication administration.,Healthcare providers should give due consideration to the patient's device feature preferences when developing a treatment plan that prescribes an inhalation device. | Previous attempts to characterise the burden of chronic respiratory diseases have focused only on specific disease conditions, such as chronic obstructive pulmonary disease (COPD) or asthma.,In this study, we aimed to characterise the burden of chronic respiratory diseases globally, providing a comprehensive and up-to-date analysis on geographical and time trends from 1990 to 2017.,Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017, we estimated the prevalence, morbidity, and mortality attributable to chronic respiratory diseases through an analysis of deaths, disability-adjusted life-years (DALYs), and years of life lost (YLL) by GBD super-region, from 1990 to 2017, stratified by age and sex.,Specific diseases analysed included asthma, COPD, interstitial lung disease and pulmonary sarcoidosis, pneumoconiosis, and other chronic respiratory diseases.,We also assessed the contribution of risk factors (smoking, second-hand smoke, ambient particulate matter and ozone pollution, household air pollution from solid fuels, and occupational risks) to chronic respiratory disease-attributable DALYs.,In 2017, 544·9 million people (95% uncertainty interval [UI] 506·9-584·8) worldwide had a chronic respiratory disease, representing an increase of 39·8% compared with 1990.,Chronic respiratory disease prevalence showed wide variability across GBD super-regions, with the highest prevalence among both males and females in high-income regions, and the lowest prevalence in sub-Saharan Africa and south Asia.,The age-sex-specific prevalence of each chronic respiratory disease in 2017 was also highly variable geographically.,Chronic respiratory diseases were the third leading cause of death in 2017 (7·0% [95% UI 6·8-7·2] of all deaths), behind cardiovascular diseases and neoplasms.,Deaths due to chronic respiratory diseases numbered 3 914 196 (95% UI 3 790 578-4 044 819) in 2017, an increase of 18·0% since 1990, while total DALYs increased by 13·3%.,However, when accounting for ageing and population growth, declines were observed in age-standardised prevalence (14·3% decrease), age-standardised death rates (42·6%), and age-standardised DALY rates (38·2%).,In males and females, most chronic respiratory disease-attributable deaths and DALYs were due to COPD.,In regional analyses, mortality rates from chronic respiratory diseases were greatest in south Asia and lowest in sub-Saharan Africa, also across both sexes.,Notably, although absolute prevalence was lower in south Asia than in most other super-regions, YLLs due to chronic respiratory diseases across the subcontinent were the highest in the world.,Death rates due to interstitial lung disease and pulmonary sarcoidosis were greater than those due to pneumoconiosis in all super-regions.,Smoking was the leading risk factor for chronic respiratory disease-related disability across all regions for men.,Among women, household air pollution from solid fuels was the predominant risk factor for chronic respiratory diseases in south Asia and sub-Saharan Africa, while ambient particulate matter represented the leading risk factor in southeast Asia, east Asia, and Oceania, and in the Middle East and north Africa super-region.,Our study shows that chronic respiratory diseases remain a leading cause of death and disability worldwide, with growth in absolute numbers but sharp declines in several age-standardised estimators since 1990.,Premature mortality from chronic respiratory diseases seems to be highest in regions with less-resourced health systems on a per-capita basis.,Bill & Melinda Gates Foundation. | 1 |
The purpose of this study was to evaluate the frequency of inadequate diagnosis and factors predictive of this in patients with chronic obstructive pulmonary disease (COPD) participating in the On-Sint study.,The On-Sint cohort was recruited for a multicenter observational study in which 356 physicians (71.6% from primary care) included adult patients who had been diagnosed with COPD.,Patients’ clinical and functional information since diagnosis and details for the recruiting physicians were collected from patient files and at the inclusion visit.,We performed a multivariate analysis to evaluate the influence of these variables on diagnostic inadequacy (absence of postbronchodilator forced expiratory volume in one second/forced vital capacity [FEV1/FVC] <0.70 or, if this value was missing, prebronchodilator FEV1/FVC <0.70).,In total, 1,214 patients were included in the study.,The patients had a mean age of 66.4±9.7 years and 78.8% were male.,In total, 51.3% of patients did not have an obstructive spirometry performed, and 21.4% had a normal or non-obstructive spirometry pattern.,Patient-related factors associated with inadequate diagnosis were: years since diagnosis (odds ratio [OR] 1.03, 95% confidence interval [CI] 1.01-1.05), number of exacerbations in the previous year (OR 1.01, 95% CI 1.01-1.02), comorbidities (OR 1.05, 95% CI 1.01-1.015), and obesity (OR 1.06, 95% CI 1.02-1.10 per kg/m2 of body mass index), while a longer smoking history (OR 0.98, 95% CI 0.97-0.99 for each pack/year) and short-acting or long-acting bronchodilator therapy (OR 0.61, 95% CI 0.44-0.76 and OR 0.46, 95% CI 0.27-0.76, respectively) were inversely related.,With regard to physician-related variables, being followed up by primary care physicians (OR 3.0, 95% CI 2.11-4.34) and in rural centers (OR 1.63, 95% CI 1.12-2.38) were positively associated with an inadequate diagnosis, while having regular follow-ups in the most severe cases (OR 0.66, 95% CI 0.46-0.93) and use of quality of life questionnaires (OR 0.55, 95% CI 0.40-0.76) were negatively associated.,Diagnosis of COPD was inadequate in half of the patients from the On-Sint cohort.,There were multiple factors, both patient-related and physician-related, associated with this misdiagnosis. | Chronic obstructive pulmonary disease (COPD) is a complex condition with pulmonary and extra-pulmonary manifestations.,This study describes the heterogeneity of COPD in a large and well characterised and controlled COPD cohort (ECLIPSE).,We studied 2164 clinically stable COPD patients, 337 smokers with normal lung function and 245 never smokers.,In these individuals, we measured clinical parameters, nutritional status, spirometry, exercise tolerance, and amount of emphysema by computed tomography.,COPD patients were slightly older than controls and had more pack years of smoking than smokers with normal lung function.,Co-morbidities were more prevalent in COPD patients than in controls, and occurred to the same extent irrespective of the GOLD stage.,The severity of airflow limitation in COPD patients was poorly related to the degree of breathlessness, health status, presence of co-morbidity, exercise capacity and number of exacerbations reported in the year before the study.,The distribution of these variables within each GOLD stage was wide.,Even in subjects with severe airflow obstruction, a substantial proportion did not report symptoms, exacerbations or exercise limitation.,The amount of emphysema increased with GOLD severity.,The prevalence of bronchiectasis was low (4%) but also increased with GOLD stage.,Some gender differences were also identified.,The clinical manifestations of COPD are highly variable and the degree of airflow limitation does not capture the heterogeneity of the disease. | 1 |
Assessing clinically important measures of disease progression is essential for evaluating therapeutic effects on disease stability in chronic obstructive pulmonary disease (COPD).,This analysis assessed whether providing additional bronchodilation with the long-acting muscarinic antagonist umeclidinium (UMEC) to patients treated with inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA) therapy would improve disease stability compared with ICS/LABA therapy alone.,This integrated post hoc analysis of four 12-week, randomized, double-blind trials (NCT01772134, NCT01772147, NCT01957163, NCT02119286) compared UMEC 62.5 µg with placebo added to open-label ICS/LABA in symptomatic patients with COPD (modified Medical Research Council dyspnea scale score ≥ 2).,A clinically important deterioration (CID) was defined as: a decrease from baseline of ≥ 100 mL in trough forced expiratory volume in 1 s (FEV1), an increase from baseline of ≥ 4 units in St George’s Respiratory Questionnaire (SGRQ) total score, or a moderate/severe exacerbation.,Risk of a first CID was evaluated in the intent-to-treat (ITT) population and in patients stratified by Global initiative for chronic Obstructive Lung Disease (GOLD) classification, exacerbation history and type of ICS/LABA therapy.,Adverse events (AEs) were also assessed.,Overall, 1637 patients included in the ITT population received UMEC + ICS/LABA (n = 819) or placebo + ICS/LABA (n = 818).,Additional bronchodilation with UMEC reduced the risk of a first CID by 45-58% in the ITT population and all subgroups analyzed compared with placebo (all p < 0.001).,Improvements were observed in reducing FEV1 (69% risk reduction; p < 0.001) and exacerbation (47% risk reduction; p = 0.004) events in the ITT population.,No significant reduction in risk of a SGRQ CID was observed.,AE incidence was similar between treatment groups.,Symptomatic patients with COPD receiving ICS/LABA experience frequent deteriorations.,Additional bronchodilation with UMEC significantly reduced the risk of CID and provided greater short-term stability versus continued ICS/LABA therapy in these patients.,GlaxoSmithKline (study number: 202067).,Plain language summary available for this article.,The online version of this article (10.1007/s12325-018-0771-4) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is a progressive disease and a composite endpoint could be an indicator of treatment effect on disease worsening.,This post-hoc analysis assessed whether indacaterol/glycopyrronium (IND/GLY) 110/50 μg once daily reduced the risk of clinically important deterioration (CID) versus salmeterol/fluticasone (SFC) 50/500 μg twice daily in moderate-to-very severe COPD patients from the FLAME study.,CID was defined as ≥100 mL decrease in forced expiratory volume in 1 s (FEV1) or ≥ 4-unit increase in St.,George’s Respiratory Questionnaire (SGRQ) total score or a moderate-to-severe COPD exacerbation.,Changes from baseline in the rate of moderate and severe exacerbations, time to first moderate-to-severe exacerbation, and change from baseline in the SGRQ score, measured after Week 12 up to Week 52, were assessed by presence of early CID (CID+) or absence of CID (CID−) at Week 12.,IND/GLY significantly delayed the time to CID (hazard ratio [HR] (95% confidence interval [CI]), 0.72 [0.67-0.78]; P < 0.0001), and reduced the incidences of CID versus SFC.,Additionally, IND/GLY delayed the time to CID in all patient subgroups.,After 12 weeks until 52 weeks, CID+ patients had a significantly higher rate of moderate-to-severe exacerbations versus CID− patients (P < 0.0001); moreover, CID+ patients experienced moderate-to-severe exacerbations significantly earlier versus CID− patients (P < 0.0001).,CID+ patients had a comparable change in the SGRQ total score versus CID− patients.,IND/GLY reduced the risk of CID versus SFC.,CID had a significant impact on long-term exacerbation outcomes in patients with moderate-to-very severe COPD and a history of ≥1 exacerbations in the previous year.,Clinicaltrials.gov NCT01782326.,The online version of this article (10.1186/s12931-018-0830-z) contains supplementary material, which is available to authorized users. | 1 |
Low mitochondrial content and oxidative capacity are well-established features of locomotor muscle dysfunction, a prevalent and debilitating systemic occurrence in patients with chronic obstructive pulmonary disease (COPD).,Although the exact cause is not firmly established, physical inactivity and oxidative stress are among the proposed underlying mechanisms.,Here, we assess the impact of COPD pathophysiology on mitochondrial DNA (mtDNA) integrity, biogenesis, and cellular oxidative capacity in locomotor muscle of COPD patients and healthy controls.,We hypothesized that the high oxidative stress environment of COPD muscle would yield a higher presence of deletion-containing mtDNA and oxidative-deficient fibers and impaired capacity for mitochondrial biogenesis.,Vastus lateralis biopsies were analyzed from 29 COPD patients and 19 healthy age-matched controls for the presence of mtDNA deletions, levels of oxidatively damaged DNA, mtDNA copy number, and regulators of mitochondrial biogenesis as well the proportion of oxidative-deficient fibers (detected histologically as cytochrome c oxidase-deficient, succinate dehydrogenase positive (COX−/SDH+ )).,Additionally, mtDNA copy number and mitochondrial transcription factor A (TFAM) content were measured in laser captured COX−SDH+ and normal single fibers of both COPD and controls.,Compared to controls, COPD muscle exhibited significantly higher levels of oxidatively damaged DNA (8-hydroxy-2-deoxyguanosine (8-OHdG) levels = 387 ± 41 vs. 258 ± 21 pg/mL) and higher prevalence of mtDNA deletions (74 vs. 15 % of subjects in each group), which was accompanied by a higher abundance of oxidative-deficient fibers (8.0 ± 2.1 vs.,1.5 ± 0.4 %).,Interestingly, COPD patients with mtDNA deletions had higher levels of 8-OHdG (457 ± 46 pg/mL) and longer smoking history (66.3 ± 7.5 years) than patients without deletions (197 ± 29 pg/mL; 38.0 ± 7.3 years).,Transcript levels of regulators of mitochondrial biogenesis and oxidative metabolism were upregulated in COPD compared to controls.,However, single fiber analyses of COX−/SDH+ and normal fibers exposed an impairment in mitochondrial biogenesis in COPD; in healthy controls, we detected a marked upregulation of mtDNA copy number and TFAM protein in COX−/SDH+ compared to normal fibers, reflecting the expected compensatory attempt by the oxidative-deficient cells to increase energy levels; in contrast, they were similar between COX−/SDH+ and normal fibers in COPD patients.,Taken together, these findings suggest that although the signaling factors regulating mitochondrial biogenesis are increased in COPD muscle, impairment in the translation of these signals prevents the restoration of normal oxidative capacity.,Single fiber analyses provide the first substantive evidence that low muscle oxidative capacity in COPD cannot be explained by physical inactivity alone and is likely driven by the disease pathophysiology. | Cigarette smoke (CS)-induced mitochondrial damage with increased reactive oxygen species (ROS) production has been implicated in COPD pathogenesis by accelerating senescence.,Mitophagy may play a pivotal role for removal of CS-induced damaged mitochondria, and the PINK1 (PTEN-induced putative kinase 1)-PARK2 pathway has been proposed as a crucial mechanism for mitophagic degradation.,Therefore, we sought to investigate to determine if PINK1-PARK2-mediated mitophagy is involved in the regulation of CS extract (CSE)-induced cell senescence and in COPD pathogenesis.,Mitochondrial damage, ROS production, and cell senescence were evaluated in primary human bronchial epithelial cells (HBEC).,Mitophagy was assessed in BEAS-2B cells stably expressing EGFP-LC3B, using confocal microscopy to measure colocalization between TOMM20-stained mitochondria and EGFP-LC3B dots as a representation of autophagosome formation.,To elucidate the involvement of PINK1 and PARK2 in mitophagy, knockdown and overexpression experiments were performed.,PINK1 and PARK2 protein levels in lungs from patients were evaluated by means of lung homogenate and immunohistochemistry.,We demonstrated that CSE-induced mitochondrial damage was accompanied by increased ROS production and HBEC senescence.,CSE-induced mitophagy was inhibited by PINK1 and PARK2 knockdown, resulting in enhanced mitochondrial ROS production and cellular senescence in HBEC.,Evaluation of protein levels demonstrated decreased PARK2 in COPD lungs compared with non-COPD lungs.,These results suggest that PINK1-PARK2 pathway-mediated mitophagy plays a key regulatory role in CSE-induced mitochondrial ROS production and cellular senescence in HBEC.,Reduced PARK2 expression levels in COPD lung suggest that insufficient mitophagy is a part of the pathogenic sequence of COPD. | 1 |
The constructs and interdependency of physical behaviors are not well described and the complexity of physical activity (PA) data analysis remains unexplored in COPD.,This study examined the interrelationships of 24-hour physical behaviors and investigated their associations with participant characteristics for individuals with mild-moderate airflow obstruction and healthy control subjects.,Vigorous PA (VPA), moderate-to-vigorous PA (MVPA), light PA (LPA), stationary time (ST), average movement intensity (vector magnitude counts per minute), and sleep duration for 109 individuals with COPD and 135 healthy controls were obtained by wrist-worn accelerometry.,Principal components analysis (PCA) examined interrelationships of physical behaviors to identify distinct behavioral constructs.,Using the PCA component loadings, linear regressions examined associations with participant (+, positive correlation; -, negative correlation), and were compared between COPD and healthy control groups.,For both groups PCA revealed ST, LPA, and average movement intensity as distinct behavioral constructs to MVPA and VPA, labeled “low-intensity movement” and “high-intensity movement,” respectively.,Sleep was also found to be its own distinct behavioral construct.,Results from linear regressions supported the identification of distinct behavioral constructs from PCA.,In COPD, low-intensity movement was associated with limitations with mobility (−), daily activities (−), health status (+), and body mass index (BMI) (−) independent of high-intensity movement and sleep.,High-intensity movement was associated with age (−) and self-care limitations (−) independent of low-intensity movement and sleep.,Sleep was associated with gender (0= female, 1= male; [−]), lung function (−), and percentage body fat (+) independent of low-intensity and high-intensity movement.,Distinct behavioral constructs comprising the 24-hour day were identified as “low-intensity movement,” “high-intensity movement,” and “sleep” with each construct independently associated with different participant characteristics.,Future research should determine whether modifying these behaviors improves health outcomes in COPD. | Multiple factors can influence the severity of chronic obstructive pulmonary disease (COPD) and the functioning of patients with COPD, such as personal characteristics and systemic manifestations.,To evaluate the different factors that can influence the activity and psychosocial impact domains of the Saint George's Respiratory Questionnaire (SGRQ) in COPD patients.,Participants, recruited in a university-based hospital, responded to the SGRQ, and in addition, personal, anthropometric, and clinical data were collected.,The study was approved by the Institutional Ethics Committee.,Data were analyzed using multiple linear regression models, with the SGRQ activity and psychosocial impact scores as outcome variables, and 10 explanatory variables (age, gender, forced expiratory volume in the first second - FEV1, smoking load, body mass index, oxygen therapy, associated diseases, regular physical activity, participation in a formal rehabilitation program, and SGRQ symptoms score) were considered.,The best regression model for predicting the SGRQ activity score (r2=0.477) included gender, FEV1, and SGRQ symptoms.,In contrast, the predictive model with the highest proportion of explained variance in psychosocial impact score (r2=0.426) included the variables gender, oxygen therapy, and SGRQ symptoms.,The results indicate that the outcomes, while based on functioning parameters in COPD patients, could be partly explained by the personal and clinical factors analyzed, especially by the symptoms assessed by the SGRQ.,Thus, it appears that the health conditions of these patients cannot be described by isolated variables, including pulmonary function parameters. | 1 |
Background: Systematic inflammation, nutritional status, and cardiovascular function have been associated with the outcomes of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) patients with heart failure (HF).,However, the value of their relevant biomarkers in predicting mortality has not been well defined yet.,We aimed to investigate the prognostic value of circulating biomarkers including C-reaction protein (CRP)/albumin (ALB), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and N-terminal pro-brain natriuretic peptide (NT-proBNP) for AECOPD patients with HF.,Methods: A retrospective study was carried out in the Second Clinical College of Jinan University from January 1, 2013 to January 31, 2019.,A total of 146 cases of AECOPD complicated with HF were enrolled and classified into survivor group (n=94) and non-survivor group (n=52).,The baseline characteristics, CRP/ALB ratio, NLR, PLR, serum levels of NT-proBNP, and other indicators were collected.,The predictors for prognosis were analyzed by multivariate logistic regression, and the ability to predict 28-day mortality was evaluated by receiver operating characteristics curve (ROC) and the area under the curve (AUC).,Results: The patients in non-survivors had significantly higher levels of CRP, CRP/ALB, NLR, PCT and NT-proBNP, but lower ALB levels compared to the survivors [111.7 (56.9, 186.5) VS.,43.8 (10.3, 96.1) mg/L, 4.6 (2.0, 8.0) VS.,1.4 (0.3, 3.4), 22.2 (11.1, 40.1) VS.,12.0 (6.2, 24.8), 2.6 (0.2, 10.3) VS.,0.08 (0.1, 0.5) ng/ml, 17912.5 (9344.0, 34344.5) VS.,9809.0 (4415.9, 16387.2) ng/ml, 25.8 (23.2, 30.5) VS.,30.7 (27.9, 34.1) g/L; P < 0.001, <0.001, 0.001, <0.001, <0.001, and < 0.001, respectively].,No significant difference in PLR was found between the two groups (P=0.413).,The logistic analysis revealed that CRP/ALB (OR=1.303, 95%CI: 1.145-1.483, P<0.001), NT-proBNP (OR=1.041, 95%CI: 1.010-1.073, P=0.009) and NLR (OR=1.010, 95%CI: 0.999-1.022, P<0.001) are independent risk factors for predicting the 28-day mortality.,The AUC of the ROC curves were 0.768, 0.767, 0.757, 0.723, 0.716, and 0.668 for CRP/ALB, PCT, CRP, NT-proBNP, ALB, and NLR, respectively.,The combination of CRP/ALB, NLR and NT-proBNP as biomarkers was shown to have better accuracy for predicting prognosis (AUC=0.830, 95%CI: 0.761-0.899, P<0.001), with a higher specificity of 80.8% and specificity of 77.7% as compared with each single biomarkers.,Conclusions: High levels of NLR, CRP/ALB and NT-proBNP may be clinical usefully predictors for death in AECOPD patients with HF.,Combination of NLR with CRP/ALB and NT-proBNP can provide a higher accuracy for predicting 28-day mortality in these patients. | Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction that is only partly reversible, inflammation in the airways, and systemic effects or comorbities.,The main cause is smoking tobacco, but other factors have been identified.,Several pathobiological processes interact on a complex background of genetic determinants, lung growth, and environmental stimuli.,The disease is further aggravated by exacerbations, particularly in patients with severe disease, up to 78% of which are due to bacterial infections, viral infections, or both.,Comorbidities include ischaemic heart disease, diabetes, and lung cancer.,Bronchodilators constitute the mainstay of treatment: β2 agonists and long-acting anticholinergic agents are frequently used (the former often with inhaled corticosteroids).,Besides improving symptoms, these treatments are also thought to lead to some degree of disease modification.,Future research should be directed towards the development of agents that notably affect the course of disease. | 1 |
Dual bronchodilator therapy is reserved as a second-line treatment in patients with chronic obstructive pulmonary disease (COPD) and provides benefits in lung function and health status versus monotherapy.,The aim of this study was to determine whether early initiation of a dual bronchodilator versus monotherapy reduced the risk of deterioration in COPD.,This post hoc pooled analysis investigated the efficacy and safety of umeclidinium/vilanterol (UMEC/VI) 62.5/25 mcg/day compared with tiotropium (TIO) 18 mcg/day in a maintenance-naïve (MN) subgroup of patients relative to the intent-to-treat (ITT) population from three 6-month active comparator studies (n = 1747).,Other treatment arms (UMEC/VI 125/25, VI 25 and UMEC 125) comprised 850 patients in total but were not included in this analysis.,The primary endpoint was trough forced expiratory volume in 1 s (FEV1).,St George’s Respiratory Questionnaire (SGRQ) score, rescue medication use, and a novel composite endpoint of short-term clinically important deterioration (CID; ≥100 ml decrease in trough FEV1, ≥4-unit increase in SGRQ score, or a COPD exacerbation) were also assessed.,UMEC/VI improved trough FEV1 versus TIO at day 169 [least squares mean (95% confidence interval): MN: 146 ml (102-189) and ITT: 95 ml (71-118); both P < 0.001].,Both UMEC/VI and TIO improved SGRQ and rescue use in the two populations, with greater improvements in rescue use with UMEC/VI versus TIO.,UMEC/VI reduced the risk of short-term clinically important deterioration versus TIO [hazard ratio; 95% confidence interval: MN: 0.66 (0.51-0.85); ITT: 0.62 (0.54-0.71), both P ≤ 0.001].,Adverse events were similar across both populations and treatments.,Early use of dual-bronchodilator therapy has superior efficacy on lung function and may reduce the risk of short-term deterioration compared to monotherapy in symptomatic patients with COPD.,Clinical trial registration: GSK analysis 202066 (NCT01316900/DB2113360, NCT01316913/DB2113374, NCT01777334/ZEP117115).,Funding: This study was funded by GSK.,The online version of this article (doi:10.1007/s12325-016-0430-6) contains supplementary material, which is available to authorized users. | Chronic obstructive pulmonary disease (COPD) is the most common chronic lung disease in the world, and its associated health burdens and costs are mounting.,Until recently, it was generally accepted that targeting the diagnosis of COPD early in its course was a relatively fruitless effort, since treatments other than already ubiquitous smoking-cessation efforts were unlikely to alter its course.,However, there is strong evidence to suggest that the majority of patients with objective COPD are not aware of their condition, and this leads to a significant delay in diagnosis, more aggressive smoking-cessation intervention, and potential treatment.,Novel methods of diagnostic testing, community health programs, and primary-care provider recommendations hold promise to expand the recognition of COPD in its incipient stages - where recent evidence suggests a rapid decline in lung function occurs and may be prevented if acted upon.,This review explores the evidence to support the efforts to justify programs aimed at early diagnosis, alternative diagnostic strategies that may augment traditional spirometry, therapeutic modalities that could potentially be used in the future to alter early lung-function decline, and emphasizes the necessary cooperative role that physicians, patients, communities, and governments need to play to realize the significant health impact that stands to be gained. | 1 |
This study aimed to evaluate the effects of vitamin D intake on COPD exacerbation and FEV1 in the patients with severe and very severe COPD.,This double blind placebo control randomized clinical trial study was done in the Ashayer university hospital in Khorramabad in 2012.,Eighty eight patients with severe and very severe COPD were randomly selected from those who recoursed to the internal medicine clinic of Ashayer hospital.,They were randomly allocated to case and placebo group.,The patients received routine treatment for COPD.,Along with the routine treatment, placebo group received 100,000 IU of oral vitamin D per month, for 6 months.,Data was analyzed using SPSS computer software, paired t-test, independent t-test, non parametric t-test and Pearson correlation coefficients.,In each group, there were 44 patients.,After the intervention, there were significant differences in FEV1 and the number of COPD exacerbation between the case and control group patients.,Also, after the study, in the case group, FEV1 was increased and the number of COPD exacerbation was decreased significantly.,Vitamin D intake decreased COPD exacerbation and improved FEV1 in the patients with severe and very severe COPD.,It is suggested that baseline serum vitamin D levels will recorded in similar studies and the effect of vitamin D intake will evaluated regarding the baseline serum vitamin D levels. | Malnutrition is a serious condition in chronic obstructive pulmonary disease (COPD).,Successful dietary intervention calls for calculations of resting metabolic rate (RMR).,One disease-specific prediction equation for RMR exists based on mainly male patients.,To construct a disease-specific equation for RMR based on measurements in underweight or weight-losing women and men with COPD, RMR was measured by indirect calorimetry in 30 women and 11 men with a diagnosis of COPD and body mass index <21 kg/m2.,The following variables, possibly influencing RMR were measured: length, weight, middle upper arm circumference, triceps skinfold, body composition by dual energy x-ray absorptiometry and bioelectrical impedance, lung function, and markers of inflammation.,Relations between RMR and measured variables were studied using univariate analysis according to Pearson.,Gender and variables that were associated with RMR with a P value <0.15 were included in a forward multiple regression analysis.,The best-fit multiple regression equation included only fat-free mass (FFM): RMR (kJ/day) = 1856 + 76.0 FFM (kg).,To conclude, FFM is the dominating factor influencing RMR.,The developed equation can be used for prediction of RMR in underweight COPD patients. | 1 |
Objective evaluation of the physical activity (PA) in patients with chronic obstructive pulmonary disease (COPD) is important.,We validated a triaxial accelerometer, Active Style Pro HJA-750C® (HJA), and evaluated the necessary conditions for obtaining reproducible data.,The PA measured by HJA was compared with that measured by two already validated accelerometers in 11 patients with COPD (age: 76.6 ± 6.9, FEV1% predicted: 57.6 ± 18.6).,Then, the influence of weather and holidays on the PA and the required number of days to obtain repeatability were examined in 21 patients with COPD (age: 73.0 ± 8.0, FEV1% predicted: 58.7 ± 19.0).,The PA values measured by HJA and those by DynaPort Move Monitor® (DMM) or Actimarker® (AM) were significantly correlated at all intensities (p=0.024 at ≥4.0 METs by DMM and p < 0.0001 at the rest) except at ≥4.0 METs by AM, though the values measured by HJA were higher than those by AM which was reported to underestimate PA.,The durations of PA on rainy days were significantly shorter than those on nonrainy days, but those on holidays were not different from those on weekdays.,The values of ICC for 3, 4, or 5 days were higher than 0.8 at all intensities.,The PA measured by HJA was correlated with the dyspnea scale FVC and age and tended to correlate with FEV1.,The HJA was validated for evaluating the PA in patients with COPD.,This trial is registered with UMIN000016363. | Multi-morbidity is common in patients with chronic obstructive pulmonary disease and low levels of physical activity are hypothesized to be an important risk factor.,The current study aimed to assess the longitudinal association between physical activity and risk of seven categories of comorbidity in chronic obstructive pulmonary disease patients.,The study included 409 patients from primary care practice in the Netherlands and Switzerland.,We assessed physical activity using the Longitudinal Ageing Study Amsterdam Physical Activity Questionnaire at baseline and followed patients for up to 5 years.,During follow-up, patients reported their comorbidities (cardiovascular, neurological, endocrine, musculoskeletal, malignant, and infectious diseases) and completed the Hospital Anxiety and Depression Scale questionnaire for mental health assessment.,We implemented multinomial logistic regression (an approximation to discrete time survival model using death as a competing risk) for our analysis.,Study results did not suggest a statistically significant association of baseline physical activity with the development of seven categories of comorbidity.,However, when we focused on depression and anxiety symptoms, we found that higher levels of physical activity at baseline were associated with a lower risk for depression (adjusted hazard ratio, 0.85; 0.75-0.95; p = 0.005) and anxiety (adjusted hazard ratio, 0.89; 0.79-1.00; p = 0.045).,In chronic obstructive pulmonary disease patients, those with high physical activity are less likely to develop depression or anxiety symptoms over time.,Increasing physical activity in chronic obstructive pulmonary disease patients may be an approach for testing to lower the burden from incident depression and anxiety.,Patients with chronic lung disease who stay physically active could reduce their chances of depression and anxiety.,Milo Puhan at the University of Zurich, Switzerland, and co-workers assessed the association between physical activity and the risk of developing various co-existing diseases in 409 patients with chronic obstructive pulmonary disease (COPD).,Co-morbidities such as cardiovascular diseases, diabetes and depression are prevalent in patients with COPD, but the reasons why are not clear.,Puhan’s team assessed patients’ activity levels using an existing questionnaire, and administered another questionnaire to assess mental health.,They followed the cohort for 5 years.,Results indicated weak associations between physical activity levels and most physical illnesses, but there were significant links between higher levels of physical activity and a reduced risk of depression and anxiety.,The results could inform novel COPD treatment programs. | 1 |
While chronic morbidity and mortality from COPD is well documented, little is known about the treatment burden faced by patients with COPD.,Patients with severe airflow obstruction (forced expiratory volume in 1 second [FEV1] <50% predicted) representing different age-groups, sex, and number of comorbidities participated in a semistructured interview.,Interviews were conducted until thematic saturation was reached.,Interviews were recorded, transcribed, and analyzed thematically using an established treatment-burden framework.,A total of 26 patients (42% male, mean age 66.7±9.8 years) with severe (n=15) or very severe (n=11) airflow limitation (mean FEV1 32.1%±9.65% predicted) were interviewed.,Participants struggled with various treatment-burden domains, predominantly with changing health behaviors, such as smoking cessation and exercise.,Interviewees often only ceased smoking after a major health event, despite being advised to do so earlier by a doctor.,Recommended exercise regimens, such as pulmonary rehabilitation classes, were curtailed, although some patients replaced them with light home-based exercise.,Interviewees had difficulty attending medical appointments, often relying on others to transport them.,Overall, COPD patients indicated they were not willing to accept the burden of treatments where they perceived minimal benefit.,This study describes the substantial treatment burden experienced by patients with COPD.,Medical advice may be rejected by patients if the benefit of following the advice is perceived as insufficient.,Health professionals need to recognize treatment burden as a source of nonadherence, and should tailor treatment discussions to fit patients’ values and capacity to achieve optimal patient outcomes. | To summarise and synthesise published qualitative studies to characterise factors that shape patient and caregiver experiences of chronic heart failure (CHF), chronic obstructive pulmonary disease (COPD) and chronic kidney disease (CKD).,Meta-review of qualitative systematic reviews and metasyntheses.,Papers analysed using content analysis.,CINAHL, EMBASE, MEDLINE, PsychINFO, Scopus and Web of Science were searched from January 2000 to April 2015.,Systematic reviews and qualitative metasyntheses where the participants were patients, caregivers and which described experiences of care for CHF, COPD and CKD in primary and secondary care who were aged ≥18 years.,Searches identified 5420 articles, 53 of which met inclusion criteria.,Reviews showed that patients' and caregivers' help seeking and decision-making were shaped by their degree of structural advantage (socioeconomic status, spatial location, health service quality); their degree of interactional advantage (cognitive advantage, affective state and interaction quality) and their degree of structural resilience (adaptation to adversity, competence in managing care and caregiver response to demands).,To the best of our knowledge, this is the first synthesis of qualitative systematic reviews in the field.,An important outcome of this overview is an emphasis on what patients and caregivers value and on attributes of healthcare systems, relationships and practices that affect the distressing effects and consequences of pathophysiological deterioration in CHF, COPD and CKD.,Interventions that seek to empower individual patients may have limited effectiveness for those who are most affected by the combined weight of structural, relational and practical disadvantage identified in this overview.,We identify potential targets for interventions that could address these disadvantages.,PROSPERO CRD42014014547. | 1 |
The purpose of this study was to assess the relationship of smoking duration with respiratory symptoms and history of chronic obstructive pulmonary disease (COPD) in the South Carolina Behavioral Risk Factor Surveillance System survey in 2012.,Data from 4,135 adults aged ≥45 years with a smoking history were analyzed using multivariable logistic regression that accounted for sex, age, race/ethnicity, education, and current smoking status, as well as the complex sampling design.,The distribution of smoking duration ranged from 19.2% (1-9 years) to 36.2% (≥30 years).,Among 1,454 respondents who had smoked for ≥30 years, 58.3% were current smokers, 25.0% had frequent productive cough, 11.2% had frequent shortness of breath, 16.7% strongly agreed that shortness of breath affected physical activity, and 25.6% had been diagnosed with COPD.,Prevalence of COPD and each respiratory symptom was lower among former smokers who quit ≥10 years earlier compared with current smokers.,Smoking duration had a linear relationship with COPD (P<0.001) and all three respiratory symptoms (P<0.001) after adjusting for smoking status and other covariates.,While COPD prevalence increased with prolonged smoking duration in both men and women, women had a higher age-adjusted prevalence of COPD in the 1-9 years, 20-29 years, and ≥30 years duration periods.,These state population data confirm that prolonged tobacco use is associated with respiratory symptoms and COPD after controlling for current smoking behavior. | Studies determining the development of a wide variety of different comorbid disorders in inflammatory arthritis (IA) patients are scarce, however, this knowledge could be helpful in optimising preventive care in IA patients.,The aim of this study is to establish the risk that new chronic comorbid disorders in newly diagnosed patients with IA in a primary care setting are developed.,This is a nested-case-control study from 2001-2010 using data from electronic medical patient records in general practice.,In total, 3,354 patients with newly diagnosed IA were selected.,Each patient was matched with two control patients of the same age and sex in the same general practice.,The development of 121 chronic comorbid disorders of index and control patients was compared using Cox regression.,After a median follow-up period of 2.8 years, 56% of the IA-patients had developed at least one chronic comorbid disorder after the onset of IA, compared to 46% of the control patients (p < 0.05).,The most frequent developed comorbid disorders after the onset of IA were of cardiovascular (23%), and musculoskeletal (17%) origin.,The highest hazard ratios (HRs) were found for anaemia (HR 2.0 [95% CI: 1.4-2.7]) osteoporosis (HR 1.9 [1.4-2.4]), and COPD (HR 1.8 [1.4-2.3]).,Patients with IA developed more chronic comorbid disorders after the onset of IA than one might expect based on age and sex.,Since comorbidity has a large impact on the disease course, quality of life, and possibly on treatment itself, prevention of comorbidity should be one of the main targets in the treatment of IA patients. | 1 |
The aim of the study was to determine the nutritional status and anthropometric values in a group of patients with COPD and to examine the relationship between these factors and disease severity.,A total of 105 COPD patients were included in this cross-sectional study.,The patients underwent spirometric exmination.,Mini nutritional assessment form was applied, and the anthropometric values of the patients were measured by bioelectrical impedance method.,Nutrient registration forms were given using a 3-day, 24-hour recall method to assess the nutrient uptake.,COPD severity was determined using the Global Initiative for Chronic Obstructive Lung Disease criteria, and the correlations between nutritional status and disease severity parameters were measured.,The prevalence of malnutrition in our patients with COPD was found to be 17%.,Spirometric parameters were found to be significantly lower in patients with low body mass index (BMI) and malnutrition.,As the modified Medical Research Council dyspnea scale score increased, the frequency of malnutrition increased (P=0.002).,Positive significant correlation was found between spirometric variables and muscle mass and fat external tissue volume of the patients.,Patients receiving higher protein content in diet showed a better muscle mass amount (P<0.001).,Our study results confirmed that malnutrition is an important and frequently encountered problem in COPD patients, and spirometric values of the patients with malnourishment and with low BMI are significantly lower.,We think that nutritional status should be evaluated in every COPD patient, and nutritional intake should be tailored individually. | Chronic obstructive pulmonary disease (COPD) is one of the top five major causes of morbidity and mortality worldwide.,Despite worldwide health care efforts, costs, and medical research, COPD figures demonstrate a continuously increasing tendency in mortality.,This is contrary to other top causes of death, such as neoplasm, accidents, and cardiovascular disease.,A major factor affecting COPD-related mortality is the acute exacerbation of COPD (AECOPD).,Exacerbations and comorbidities contribute to the overall severity in individual patients.,Despite the underestimation by the physicians and the patients themselves, AECOPD is a really devastating event during the course of the disease, similar to acute myocardial infarction in patients suffering from coronary heart disease.,In this review, we focus on the evidence that supports the claim that AECOPD is the “stroke of the lungs”.,AECOPD can be viewed as: a Semicolon or disease’s full-stop period, Triggering a catastrophic cascade, usually a Relapsing and Overwhelming event, acting as a Killer, needing Emergent treatment. | 1 |
This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | COPD is a common complex disease characterized by progressive airflow limitation.,Several genome-wide association studies (GWASs) have discovered genes that are associated with COPD.,Recently, candidate genes for COPD identified by GWASs include CHRNA3/5 (cholinergic nicotine receptor alpha 3/5), IREB2 (iron regulatory binding protein 2), HHIP (hedgehog-interacting protein), FAM13A (family with sequence similarity 13, member A), and AGER (advanced glycosylation end product-specific receptor).,Their association with COPD susceptibility has been replicated in multiple populations.,Since these candidate genes have not been considered in COPD, their pathological roles are still largely unknown.,Herein, we review some evidences that they can be effective drug targets or serve as biomarkers for diagnosis or subtyping.,However, more study is required to understand the functional roles of these candidate genes.,Future research is needed to characterize the effect of genetic variants, validate gene function in humans and model systems, and elucidate the genes’ transcriptional and posttranscriptional regulatory mechanisms. | 1 |
Adherence to inhaled medications by COPD patients is a challenging issue, but relatively understudied.,The aim of this study is the characterization of adherence to inhaled medications by COPD patients, with a focus on patient-related determinants.,Stable COPD outpatients ≥40 years of age from a respiratory unit and diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease criteria were included in a cross-sectional study.,The Measure of Treatment Adherence (MTA), the Beliefs about Medications Questionnaire (BMQ) and demographic, clinical, and COPD questionnaires were used.,After completing these questionnaires, semi-structured interviews were carried out and participants were encouraged to justify their opinions and behaviors.,Field notes were made during the interviews and each interview was analyzed before the next one.,Quantitative and qualitative analyses of the variables were then performed.,A total of 300 out of 319 participants (mean age =67.7 years, 78.1% males) completed the MTA questionnaire.,Of these, 31.3% were considered poorly adherent and 16.7% as non-adherent to the inhaled therapy.,A statistically significant negative association was found between adherence and current smoking status (P=0.044), and between adherence and FEV1% (P=0.000).,The mean BMQ Necessity score was higher in adherent patients (P=0.000), but the the mean Concern score was similar for both (P=0.877).,We found nine patterns of poor-adherence, six reasons given for poor-adherence behaviors, five reasons for good-adherence behaviors and three patient-related domains on adherence to medications.,Adherence is related to need perception and to the functional severity of the disease.,A non-adherent patient is usually a current smoker with lower degree of airflow limitation and lower perception of medication necessity.,New information obtained was related to the patterns and reasons for different adherence behaviors, which are based on three major groups of patient related-determinants: health-related experiences, health-related behaviors and health-related beliefs. | Poor inhaler technique and nonadherence impair the efficacy of medications for asthma and chronic obstructive pulmonary disease (COPD).,A range of factors, including age, dexterity, inspiratory capacity, cognitive ability, health literacy, and ethnicity, can impact a patient's ability and intention to use their device.,Treatment success can also be influenced by patient preferences and perceptions.,Therefore, it is important that healthcare professionals effectively match inhaler devices to individual patients' needs and abilities and empower patients by including them in treatment decisions.,Physicians must, therefore, fully understand the characteristics of each device, as well as their patients' demographic characteristics and comorbidities.,Following device selection, patient training and education, including a physical demonstration of the device, are key to eliminate any critical errors that may impact on health outcomes.,Inhaler technique should be frequently rechecked.,This review will examine the important role of primary care providers in the selection of appropriate inhaler devices and provision of training for patients with COPD and asthma to optimize correct inhaler use and adherence.,An overview of the key features of available devices and of the factors to consider when selecting devices will be provided in the context of current asthma and COPD guidelines. | 1 |
Although it is known that patients with chronic obstructive pulmonary disease (COPD) generally do have an increased heart rate, the effects on both mortality and non-fatal pulmonary complications are unclear.,We assessed whether heart rate is associated with all-cause mortality, and non-fatal pulmonary endpoints.,A prospective cohort study of 405 elderly patients with COPD was performed.,All patients underwent extensive investigations, including electrocardiography.,Follow-up data on mortality were obtained by linking the cohort to the Dutch National Cause of Death Register and information on complications (exacerbation of COPD or pneumonia) by scrutinizing patient files of general practitioners.,Multivariable cox regression analysis was performed.,During the follow-up 132 (33%) patients died.,The overall mortality rate was 50/1000 py (42-59).,The major causes of death were cardiovascular and respiratory.,The relative risk of all-cause mortality increased with 21% for every 10 beats/minute increase in heart rate (adjusted HR: 1.21 [1.07-1.36], p = 0.002).,The incidence of major non-fatal pulmonary events was 145/1000 py (120-168).,The risk of a non-fatal pulmonary complication increased non-significantly with 7% for every 10 beats/minute increase in resting heart rate (adjusted HR: 1.07 [0.96-1.18], p = 0.208).,Increased resting heart rate is a strong and independent risk factor for all-cause mortality in elderly patients with COPD.,An increased resting heart rate did not result in an increased risk of exacerbations or pneumonia.,This may indicate that the increased mortality risk of COPD is related to non-pulmonary causes.,Future randomized controlled trials are needed to investigate whether heart-rate lowering agents are worthwhile for COPD patients. | The association between disease markers and health status (HS) overtime is unclear.,The aim of this study was to verify the predictors of HS at baseline and after three years in Chronic Obstructive Pulmonary Disease (COPD) patients.,Ninety-five consecutive COPD patients (66% male, age = 67 ± 9 y, FEV1 = 58 ± 23%) underwent the following evaluations at baseline and after three years: body composition, pulse oximetry (SpO2), six-minute walk distance (6MWD), Modified edical Research Council dyspnea scale (MMRC) and Saint George's Respiratory Questionnaire (SGRQ).,The Charlson comorbidity index and BODE index were calculated.,COPD exacerbations during the follow-up were evaluated.,At baseline, age, gender, smoking, SpO2, BODE index or its components (BMI, MMRC, FEV1 and 6MWD), and Charlson index were included in a multiple linear regression analysis with the baseline SGRQ total score as the dependent variable.,After three years, we included the final values of the variables plus the number of exacerbations and the final SGRQ total score as the dependent variable.,SGRQ total score (42 ± 19% vs 44 ± 19%; p = 0.041) and activity domain (52 ± 21% vs 60 ± 22%; p < 0.001) deteriorated during follow-up.,At baseline, BODE index was selected as a predictor of SGRQ total score (R2 = 0.46; p < 0.001); after three years, BODE index and age were the predictors (R2 = 0.49; p < 0.001).,When the BODE index was replaced by its variables, MMRC was selected as the only variable associated with the SGRQ total score (R2 = 0.58; p < 0.001).,After three years, MMRC, FEV1 and number of exacerbations were selected as predictors of SGRQ total score (R2 = 0.63; p < 0.001).,HS deteriorated significantly over the three-year period and the predictors of HS do not change over time.,BODE index and dyspnea were predictors at baseline and after three years.,Exacerbation was also a predictor of HS after three years.,ClinicalTrials.gov: NCT00605540 | 1 |
Arformoterol is the (R,R)-enantiomer of formoterol.,Preclinical studies suggest that it is a stronger bronchodilator than the racemic (R,R/S,S)-formoterol; however, its potential clinical advantages have not been demonstrated.,This study compared the length of stay (LOS), 30-day readmission rates, and doses of rescue medication administered in hospitalized patients with COPD who were treated with nebulized arformoterol or nebulized formoterol.,This retrospective analysis utilized data from Premier, Inc.,(Charlotte, NC, USA), the largest nationwide hospital-based administrative database.,COPD patients ≥40 years of age were included if they were hospitalized between January 2011 and July 2014, had no asthma diagnoses, and were treated with nebulized arformoterol or nebulized formoterol.,LOS was measured from the day the patients initiated the study medication (index day).,Rescue medications were defined as short-acting bronchodilators used from the index day onward.,Multivariate statistical models included a random effect for hospital and controlled for patient demographics, hospital characteristics, admission characteristics, prior hospitalizations, comorbidities, pre-index service use, and pre-index medication use.,A total of 7,876 patients received arformoterol, and 3,612 patients received nebulized formoterol.,There was no significant difference in 30-day all-cause (arformoterol =11.9%, formoterol =12.1%, odds ratio [OR] =0.981, P=0.82) or COPD-related hospital readmission rates (arformoterol =8.0%, formoterol =8.0%, OR =1.002, P=0.98) after adjusting for covariates.,The adjusted mean LOS was significantly shorter for arformoterol-treated vs formoterol-treated patients (4.6 vs 4.9 days, P=0.039), and arformoterol-treated patients used significantly fewer doses of rescue medications vs formoterol-treated patients (5.9 vs 6.6 doses, P=0.006).,During inpatient stays, treating with arformoterol instead of nebulized formoterol may lead to shorter LOS and lower rescue medication use. | Multimorbidity, the presence of 2 or more chronic conditions, frequently affects people with chronic obstructive pulmonary disease (COPD).,Many have high-cost, highly complex conditions that have a substantial impact on state Medicaid programs.,We quantified the cost of Medicaid-insured patients with COPD co-diagnosed with other chronic disorders.,We used nationally representative Medicaid claims data to analyze the impact of comorbidities (other chronic conditions) on the disease burden, emergency department (ED) use, hospitalizations, and total health care costs among 291,978 adult COPD patients.,We measured the prevalence of common conditions and their influence on COPD-related and non-COPD-related resource use by using the Elixhauser Comorbidity Index.,Elixhauser comorbidity counts were clustered from 0 to 7 or more.,We performed multivariable logistic regression to determine the odds of ED visits by Elixhauser scores adjusting for age, sex, race/ethnicity, and residence.,Acute care, hospital bed days, and total Medicaid-reimbursed costs increased as the number of comorbidities increased.,ED visits unrelated to COPD were more common than visits for COPD, especially in patients self-identified as black or African American (designated black).,Hypertension, diabetes, affective disorders, hyperlipidemia, and asthma were the most prevalent comorbid disorders.,Substance abuse, congestive heart failure, and asthma were commonly associated with ED visits for COPD.,Female sex was associated with COPD-related and non-COPD-related ED visits.,Comorbidities markedly increased health services use among people with COPD insured with Medicaid, although ED visits in this study were predominantly unrelated to COPD.,Achieving excellence in clinical practice with optimal clinical and economic outcomes requires a whole-person approach to the patient and a multidisciplinary health care team. | 1 |
The prevalence of disabilities is rising steadily, reflecting an aging population and an increasing burden of chronic conditions affecting quality of life.,There are scant national data on the prevalence of disability among individuals with chronic obstructive pulmonary disease (COPD).,The main objective was to estimate the prevalence of common disabilities among US-based individuals diagnosed with COPD.,Data from the BRFSS, a national telephone survey examining health-related behaviors in 2016-2017 were analyzed.,The study population consisted of individuals with self-reported COPD (N = 38352 in 2016 and N = 35423 in 2017).,The prevalence of disabilities in hearing, vision, cognition, mobility, and independent living were obtained and adjusted with sampling weights.,Healthcare access measures were described by type of disability.,Mobility disability had the highest prevalence of 45.9 (44.8-47.0) % in 2016 and 48.4 (47.3-49.5) % in 2017 among respondents with COPD.,The prevalence of disabilities was highest among those 45-64 years old, except for hearing and cognition.,Hearing disabilities were most prevalent among males with COPD while cognitive and mobility disabilities were most prevalent among females with COPD.,While differences in the prevalence of disabilities were observed, access to health care was similar by disability type and age group among respondents.,Contrary to expectation, the highest prevalence of disabilities was found not to be among those 65 years old and above.,Further research is needed to explain this age-specific shift in the burden of disability, as long-term care planning and prevention support systems should be informed by the demographical patterns of disabilities among individuals with COPD. | COPD is a disease associated with significant economic burden.,It was reported that Global initiative for chronic Obstructive Lung Disease (GOLD) guideline-oriented pharmacotherapy improves airflow limitation and reduces health care costs.,However, several studies showed a significant dissociation between international recommendations and clinicians’ practices.,The consequent reduced diagnostic and therapeutic inappropriateness has proved to be associated with an increase in costs and a waste of economic resources in the health sector.,The aim of the study was to evaluate COPD management in the Puglia region.,The study was performed in collaboration with the pulmonology centers and the Regional Health Agency (AReS Puglia).,An IT platform allowed the pulmonologists to enter data via the Internet.,All COPD patients who visited a pneumological outpatient clinic for the first time or for regular follow-ups or were admitted to a pneumological department for an exacerbation were considered eligible for the study.,COPD’s diagnosis was confirmed by a pulmonologist at the moment of the visit.,The project lasted 18 months and involved 17 centers located in the Puglia region.,Six hundred ninety-three patients were enrolled, evenly distributed throughout the region.,The mean age was 71±9 years, and 85% of them were males.,Approximately 23% were current smokers, 63% former smokers and 13.5% never smokers.,The mean post-bronchodilator forced expiratory volume in 1 second was 59%±20% predicted.,The platform allowed the classification of patients according to the GOLD guidelines (Group A: 20.6%, Group B: 32.3%, Group C: 5.9% and Group D: 39.2%), assessed the presence and severity of exacerbations (20% of the patients had an exacerbation defined as mild [13%], moderate [37%] and severe [49%]) and evaluated the appropriateness of inhalation therapy at the time of the visit.,Forty-nine percent of Group A patients were following inappropriate therapy; in Group B, 45.8% were following a therapy in contrast with the guidelines.,Among Group C patients, 41.46% resulted in triple combination therapy, whilê14% of Group D patients did not have a therapy or were following an inappropriate therapy.,In conclusion, 30% of all patients evaluated had been following an inadequate therapy.,Subsequently, an online survey was developed to inquire about the reasons for the results obtained.,In particular, we investigated the reasons why 30% of our population did not follow the therapy suggested by the GOLD guidelines: 1) why was there an excessive use of inhaled corticosteroids, 2) why a significantly high percentage was inappropriately treated with triple therapy and 3) why a consistent percentage (11%) of Group D patients were not treated at all.,The data provides an overview on the management of COPD in the region of Puglia (Italy) and represents a resource in order to improve appropriateness and reduce the waste of health resources. | 1 |
The morning tends to be the most difficult time of day for many patients with chronic obstructive pulmonary disease (COPD) when symptoms can limit one’s ability to perform even simple activities.,Morning symptoms have been linked to higher levels of work absenteeism, thereby increasing the already substantial economic burden associated with COPD.,A validated patient-reported outcome (PRO) instrument designed to capture morning symptoms will allow for a more comprehensive approach to the evaluation of treatment benefit in COPD clinical trials.,A qualitative interview study was conducted among a sample of symptomatic adults with COPD.,Concept elicitation interviews (n = 35) were conducted to identify COPD morning symptoms, followed by cognitive interviews (n = 21) to ensure patient comprehension of the items, instructions and response options of the draft COPD Morning Symptom Diary (COPD-MSD).,All interview transcript data were coded using ATLAS.ti software for content analysis.,Mean age of the concept elicitation and cognitive interview sample was 65.0 years (±7.5) and 62.3 years (±8.3), respectively.,The study sample represented the full range of COPD severity (Global Initiative for Chronic Lung Disease [GOLD] classifications I-IV) and included a mix of racial backgrounds, employment status and educational achievement.,During the concept elicitation interviews, the three most frequently reported morning symptoms were shortness of breath (n = 35/35; 100 %), phlegm/mucus (n = 31/35; 88.6 %), and cough (n = 30/35; 85.7 %).,A group of clinical and instrument development experts convened to review the concept elicitation data and develop the initial 32-item draft COPD-MSD.,Cognitive interviews indicated subjects found the draft COPD-MSD to be comprehensive, clear, and easy to understand.,The COPD-MSD underwent minor editorial revisions and streamlining based on cognitive interviews and input from the experts to yield the final 19-item daily diary.,This study supports the content validity of the new COPD-MSD and positions the diary for quantitative psychometric testing. | Aclidinium/formoterol is a twice-daily (BID) fixed-dose combination (FDC) in development for chronic obstructive pulmonary disease (COPD).,The efficacy and safety of aclidinium/formoterol versus monotherapy and placebo in patients with COPD was assessed.,In this 24-week double-blind, parallel-group, active- and placebo-controlled, multicentre Phase III study, patients (≥40 years, post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity <70% and FEV1 ≥30% but <80% predicted normal) were randomised 2:2:2:2:1 to aclidinium/formoterol 400/12 μg (n = 385) or 400/6 μg (n = 381), aclidinium 400 μg (n = 385), formoterol 12 μg (n = 384) or placebo (n = 194) BID via Genuair®/Pressair®a.,At Week 24, aclidinium/formoterol 400/12 μg and 400/6 μg lead to significant improvements from baseline in 1-hour post-dose FEV1 versus aclidinium (125 mL [95% CI: 90, 160; p < 0 · 001] and 69 mL [95% CI: 34, 105; p < 0.001], respectively) and trough FEV1 versus formoterol (85 mL [95% CI: 51, 119; p < 0.001] and 53 mL [95% CI: 19, 87; p < 0.01], respectively; co-primary endpoints).,Additionally, aclidinium/formoterol 400/12 μg and 400/6 μg provided significant improvements in Transition Dyspnoea Index (TDI) focal score versus placebo (1.29 units [95% CI: 0.73, 1.86; p < 0.001] and 1.16 units [95% CI: 0.59, 1.73; p < 0.001], respectively; secondary endpoint).,All treatments were well tolerated, with safety profiles of the FDCs similar to those of placebo and monotherapy.,Both aclidinium/formoterol BID doses significantly improved bronchodilation versus monotherapy, and dyspnoea versus placebo, with no increase in safety risk.,Aclidinium/formoterol may be an effective treatment for patients with COPD.,ClinicalTrials.gov: NCT01462942.,The online version of this article (doi:10.1186/1471-2466-14-178) contains supplementary material, which is available to authorized users. | 1 |
A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and untreated even though they may have a burden of respiratory symptoms that impact quality of life.,The OCEAN study assessed the ability of screening questionnaires to identify individuals with, or at risk of, COPD by comparing questionnaire outcomes with spirometric measures of lung function.,This observational study included participants ≥40 years of age presenting for their annual health examination at a single medical center in Okinawa, Japan.,Participants completed COPD screening questionnaires (CAPTURE and COPD-Q), the Chronic Airways Assessment Test (CAAT), and general demographic and health-related questionnaires.,The performance characteristics of CAPTURE and COPD-Q were compared with spirometry-based airflow limitation by calculating the area under the receiver operating characteristic (ROC-AUC) curve.,A total of 2518 participants were included in the study; 79% of whom were <60 years of age (mean 52.0 years).,A total of 52 (2.1%) participants had airflow limitation defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7, and 420 (16.7%) participants were classified as Preserved Ratio Impaired Spirometry (PRISm).,Among participants with PRISm, 75 (17.9%) had a CAAT total score ≥10.,Airflow limitation and PRISm were more prevalent in current smokers versus past smokers.,For the CAPTURE questionnaire, ROC-AUC for screening airflow limitation, PRISm, and PRISm with a CAAT total score ≥10 were 0.59, 0.55, and 0.69, respectively; for COPD-Q, these three clinical features were 0.67, 0.58 and 0.68, respectively.,This study demonstrated that CAPTURE and COPD-Q appear to be effective screening tools for identifying symptomatic individuals with undiagnosed, or at risk of developing COPD in adults ≥40 years of age in Okinawa.,Furthermore, early diagnosis and management of PRISm is important to improve future outcomes and the societal burden of disease. | COPD patients suffer from respiratory symptoms and limitations in daily life.,We aimed to characterize the impact of disease on overall health, daily life, and perceived well-being in COPD outpatients.,We conducted a national, cross-sectional study among pulmonologists and general practitioners (GPs).,The St.,George’s Respiratory Questionnaire for COPD patients (SGRQ-C) was used.,Inclusion criteria were a physician’s diagnosis of COPD and age ≥40 years.,Subjects with a history of lung surgery, lung cancer or COPD exacerbation within the last four weeks were excluded.,Sixty-seven pulmonologists and 6 GPs enrolled 1175 COPD patients.,Two hundred forty-eight of those did not fulfill GOLD criteria for COPD (FEV1/FVC <0.7) and 77 were excluded due to missing data.,Finally, 850 patients (62.8% men; mean age 66.2 ± 0.3 (SE) years; mean FEV1%pred.,51.5 ± 0.6 (SE)) were analyzed.,Last year, 55.4% reported at least one exacerbation, and 12.7% were hospitalized for COPD exacerbation.,Mean SGRQ-C total score was 43.1 ± 0.83 (SE) and mean component scores for symptoms, activity and impacts were 55.6, 55.4 and 30.5, respectively.,Half of the patients (50.3%) reported not being able to do any sports and 78.7% stated that their respiratory symptoms did not allow them doing anything they would like to do.,In patients with less severe COPD (FEV1pred ≥50% and non-frequent exacerbations), global health status was overrated, ie, estimated as better by the physician than by the patient, while it was underrated in more severe COPD.,In Austria, the burden of disease in COPD outpatients tends to be underestimated in patients with milder airway obstruction and less exacerbations and overestimated in patients with more severe airway obstruction and frequent exacerbations.,Our finding suggests that validated assessment of global health status might decrease these differences of perception. | 1 |
Non-typeable Haemophilus influenzae (NTHi) is a key pathogen in COPD, being associated with airway inflammation and risk of exacerbation.,Why some patients are susceptible to colonisation is not understood.,We hypothesised that this susceptibility may be due to a deficiency in mucosal humoral immunity.,The aim of our study (NCT01701869) was to quantify the amount and specificity of antibodies against NTHi in the lungs and the associated risk of infection and inflammation in health and COPD.,Phlebotomy, sputum induction and bronchoscopy were performed on 24 mild-to-moderate COPD patients and 8 age and smoking-matched controls.,BAL (Bronchoalveolar lavage) total IgG1, IgG2, IgG3, IgM and IgA concentrations were significantly increased in COPD patients compared to controls.,NTHi was detected in the lungs of 7 of the COPD patients (NTHi+ve-29%) and these patients had a higher median number of previous exacerbations than NTHi-ve patients as well as evidence of increased systemic inflammation.,When comparing NTHi+ve versus NTHi-ve patients we observed a decrease in the amount of both total IgG1 (p = 0.0068) and NTHi-specific IgG1 (p = 0.0433) in the BAL of NTHi+ve patients, but no differences in total IgA or IgM.,We observed no evidence of decreased IgG1 in the serum of NTHi+ve patients, suggesting this phenomenon is restricted to the airway.,Furthermore, the NTHi+ve patients had significantly greater levels of IL-1β (p = 0.0003), in BAL than NTHi-ve COPD patients.This study indicates that the presence of NTHi is associated with reduced levels and function of IgG1 in the airway of NTHi-colonised COPD patients.,This decrease in total and NTHI-specific IgG1 was associated with greater systemic and airway inflammation and a history of more frequent exacerbations and may explain the susceptibility of some COPD patients to the impacts of NTHi. | Although culture-independent techniques have shown that the lungs are not sterile, little is known about the lung microbiome in chronic obstructive pulmonary disease (COPD).,We used pyrosequencing of 16S amplicons to analyze the lung microbiome in two ways: first, using bronchoalveolar lavage (BAL) to sample the distal bronchi and air-spaces; and second, by examining multiple discrete tissue sites in the lungs of six subjects removed at the time of transplantation.,We performed BAL on three never-smokers (NS) with normal spirometry, seven smokers with normal spirometry (“heathy smokers”, HS), and four subjects with COPD (CS).,Bacterial 16 s sequences were found in all subjects, without significant quantitative differences between groups.,Both taxonomy-based and taxonomy-independent approaches disclosed heterogeneity in the bacterial communities between HS subjects that was similar to that seen in healthy NS and two mild COPD patients.,The moderate and severe COPD patients had very limited community diversity, which was also noted in 28% of the healthy subjects.,Both approaches revealed extensive membership overlap between the bacterial communities of the three study groups.,No genera were common within a group but unique across groups.,Our data suggests the existence of a core pulmonary bacterial microbiome that includes Pseudomonas, Streptococcus, Prevotella, Fusobacterium, Haemophilus, Veillonella, and Porphyromonas.,Most strikingly, there were significant micro-anatomic differences in bacterial communities within the same lung of subjects with advanced COPD.,These studies are further demonstration of the pulmonary microbiome and highlight global and micro-anatomic changes in these bacterial communities in severe COPD patients. | 1 |
We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting β2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels ≥2% were associated with a greater reduction in exacerbation rates with ICS therapy.,Three studies of ≥1-year duration met the inclusion criteria.,Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs ≥2%).,At baseline, 57-75% of patients had ≥2% blood eosinophils.,Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level.,For patients with ≥2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001).,No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively).,In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo).,No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ.,Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. | The optimal use of various therapeutic combinations for moderate/severe chronic obstructive pulmonary disease (COPD) is unclear.,The GLISTEN trial compared the efficacy of two long-acting anti-muscarinic antagonists (LAMA), when combined with an inhaled corticosteroid (ICS) and a long-acting β2 agonist (LABA).,This randomised, blinded, placebo-controlled trial in moderate/severe COPD patients compared once-daily glycopyrronium (GLY) 50 µg, once-daily tiotropium (TIO) 18 µg or placebo (PLA), when combined with salmeterol/fluticasone propionate (SAL/FP) 50/500 µg twice daily.,The primary objective was to determine the non-inferiority of GLY+SAL/FP versus TIO+SAL/FP on trough FEV1 after 12 weeks.,An important secondary objective was whether addition of GLY to SAL/FP was better than SAL/FP alone.,773 patients (mean FEV1 57.2% predicted) were randomised; 84.9% completed the trial.,At week 12, GLY+SAL/FP demonstrated non-inferiority to TIO+SAL/FP for trough FEV1: least square mean treatment difference (LSMdiff) −7 mL (SE 17.4) with a lower limit for non-inferiority of −60 mL.,There was significant increase in week 12 trough FEV1 with GLY+SAL/FP versus PLA+SAL/FP (LSMdiff 101 mL, p<0.001).,At 12 weeks, GLY+SAL/FP produced significant improvement in St George's Respiratory Questionnaire total score versus PLA+SAL/FP (LSMdiff −2.154, p=0.02).,GLY+SAL/FP demonstrated significant rescue medication reduction versus PLA+SAL/FP (LSMdiff −0.72 puffs/day, p<0.001).,Serious adverse events were similar for GLY+SAL/FP, TIO+SAL/FP and PLA+SAL/FP with an incidence of 5.8%, 8.5% and 5.8%, respectively.,GLY+SAL/FP showed comparable improvements in lung function, health status and rescue medication to TIO+SAL/FP.,Importantly, addition of GLY to SAL/FP demonstrated significant improvements in lung function, health status and rescue medication compared to SAL/FP.,NCT01513460. | 1 |
COPD is the third leading cause of death in the world and its global burden is predicted to increase further.,Even though the prevalence of COPD is well studied, only few studies examined the incidence of COPD in a prospective and standardized manner.,In a prospective population-based cohort study (Rotterdam Study) enrolling subjects aged ≥45, COPD was diagnosed based on a pre-bronchodilator obstructive spirometry (FEV1/FVC < 0.70).,In absence of an interpretable spirometry within the Rotterdam Study, cases were defined as having COPD diagnosed by a physician on the basis of clinical presentation and obstructive lung function measured by the general practitioner or respiratory physician.,Incidence rates were calculated by dividing the number of incident cases by the total number of person years of subjects at risk.,In this cohort of 14,619 participants, 1993 subjects with COPD were identified of whom 689 as prevalent ones and 1304 cases as incident ones.,The overall incidence rate (IR) of COPD was 8.9/1000 person-years (PY); 95 % Confidence Interval (CI) 8.4-9.4.,The IR was higher in males and in smokers.,The proportion of female COPD participants without a history of smoking was 27.2 %, while this proportion was 7.3 % in males.,The prevalence of COPD in the Rotterdam Study is 4.7 % and the overall incidence is approximately 9/1000 PY, with a higher incidence in males and in smokers.,The proportion of never-smokers among female COPD cases is substantial.,The online version of this article (doi:10.1007/s10654-016-0132-z) contains supplementary material, which is available to authorized users. | Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin.,Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues.,Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA).,Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines.,Eosinophils are the major source of interleukin-5 and highly express the interleukin-5Rα on their surface.,Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5Rα (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD).,Overall, targeting interleukin-5/interleukin-5Rα is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma.,Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA.,A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD.,The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD.,Interleukin-5/interleukin-5Rα-targeted treatments offer promises to patients with eosinophilic respiratory disorders. | 1 |
The Global Initiative of Chronic Obstructive Lung Disease (GOLD) guidelines define chronic obstructive pulmonary disease (COPD) in subjects with FEV1/FVC <0.7.,However, the use of this fixed ratio may result in over-diagnosis of COPD in the elderly, especially with mild degree of COPD.,The lower limit of normal (LLN) can be used to minimize the potential misclassification.,The aim of this study was to evaluate the impact of different definitions of airflow obstruction (LLN or fixed ratio of FEV1/FVC) on the estimated prevalence of COPD in a population-based sample.,We compared the prevalence of COPD and its difference diagnosed by different methods using either fixed ratio (FEV1/FVC <0.7) or LLN criterion (FEV1/FVC below LLN).,Among the 4,816 subjects who had performed spirometry, 2,728 subjects met new ATS/ERS spirometry criteria for acceptability and repeatability.,The prevalence of COPD was 10.9% (14.7% in men, 7.2% in women) by LLN criterion and 15.5% (21.8% in men, 9.1% in women) by fixed ratio of FEV1/FVC among subjects older than 45 yr.,The difference of prevalence between LLN and fixed ratio of FEV1/FVC was even higher among subjects with age ≥65, 14.9% and 31.1%, respectively.,In conclusion, the prevalence of COPD by LLN criterion was significantly lower in elderly compared to fixed ratio of FEV1/FVC.,Implementing LLN criterion instead of fixed ratio of FEV1/FVC may reduce the risk of over-diagnosis of COPD in elderly people. | Lung function and exacerbations of chronic obstructive pulmonary disease (COPD) have been associated with short-term exposure to air pollution.,However, the effect of long-term exposure to particulate matter from industry and traffic on COPD as defined by lung function has not been evaluated so far.,Our study was designed to investigate the influence of long-term exposure to air pollution on respiratory symptoms and pulmonary function in 55-year-old women.,We especially focused on COPD as defined by GOLD criteria and additionally compared the effects of air pollution on respiratory symptoms by questionnaire data and by lung function measurements.,In consecutive cross sectional studies conducted between 1985-1994, we investigated 4757 women living in the Rhine-Ruhr Basin of Germany.,NO2 and PM10 exposure was assessed by measurements done in an 8 km grid, and traffic exposure by distance from the residential address to the nearest major road using Geographic Information System data.,Lung function was determined and COPD was defined by using the GOLD criteria.,Chronic respiratory symptoms and possible confounders were defined by questionnaire data.,Linear and logistic regressions, including random effects were used to account for confounding and clustering on city level.,The prevalence of COPD (GOLD stages 1-4) was 4.5%.,COPD and pulmonary function were strongest affected by PM10 and traffic related exposure.,A 7 μg/m3 increase in five year means of PM10 (interquartile range) was associated with a 5.1% (95% CI 2.5%-7.7%) decrease in FEV1, a 3.7% (95% CI 1.8%-5.5%) decrease in FVC and an odds ratio (OR) of 1.33 (95% CI 1.03-1.72) for COPD.,Women living less than 100 m from a busy road also had a significantly decreased lung function and COPD was 1.79 times more likely (95% CI 1.06-3.02) than for those living farther away.,Chronic symptoms as based on questionnaire information showed effects in the same direction, but less pronounced.,Chronic exposure to PM10, NO2 and living near a major road might increase the risk of developing COPD and can have a detrimental effect on lung function. | 1 |
The first changes associated with smoking are in the small airway epithelium (SAE).,Given that smoking alters SAE gene expression, but only a fraction of smokers develop chronic obstructive pulmonary disease (COPD), we hypothesized that assessment of SAE genome-wide gene expression would permit biologic phenotyping of the smoking response, and that a subset of healthy smokers would have a “COPD-like” SAE transcriptome.,SAE (10th-12th generation) was obtained via bronchoscopy of healthy nonsmokers, healthy smokers and COPD smokers and microarray analysis was used to identify differentially expressed genes.,Individual responsiveness to smoking was quantified with an index representing the % of smoking-responsive genes abnormally expressed (ISAE), with healthy smokers grouped into “high” and “low” responders based on the proportion of smoking-responsive genes up- or down-regulated in each smoker.,Smokers demonstrated significant variability in SAE transcriptome with ISAE ranging from 2.9 to 51.5%.,While the SAE transcriptome of “low” responder healthy smokers differed from both “high” responders and smokers with COPD, the transcriptome of the “high” responder healthy smokers was indistinguishable from COPD smokers.,The SAE transcriptome can be used to classify clinically healthy smokers into subgroups with lesser and greater responses to cigarette smoking, even though these subgroups are indistinguishable by clinical criteria.,This identifies a group of smokers with a “COPD-like” SAE transcriptome. | One hundred million deaths were caused by tobacco in the 20th century, and it is estimated that there will be up to one billion deaths attributed to tobacco use in the 21st century.,Chronic obstructive pulmonary disease (COPD) is rapidly becoming a global public health crisis with smoking being recognized as its most important causative factor.,The most effective available treatment for COPD is smoking cessation.,There is mounting evidence that the rate of progression of COPD can be reduced when patients at risk of developing the disease stop smoking, while lifelong smokers have a 50% probability of developing COPD during their lifetime.,More significantly, there is also evidence that the risk of developing COPD falls by about half with smoking cessation.,Several pharmacological interventions now exist to aid smokers in cessation; these include nicotine replacement therapy, bupropion, and varenicline.,All pharmacotherapies for smoking cessation are more efficacious than placebo, with odds ratios of about 2.,Pharmacologic therapy should be combined with nonpharmacologic (behavioral) therapy.,Unfortunately, despite the documented efficacy of these agents, the absolute number of patients who are abstinent from smoking at 12 months of follow-up is low. | 1 |
This study assessed the effects of inhaled corticosteroid (ICS) on airway vascular remodeling in chronic obstructive pulmonary disease (COPD).,Thirty-four subjects with mild-to-moderate COPD were randomly allocated 2:1 to ICS or placebo treatment in a double-blinded clinical trial over 6 months.,Available tissue was compared before and after treatment for vessel density, and expression of VEGF, TGF-β1, and TGF-β1-related phosphorylated transcription factors p-SMAD 2/3.,This clinical trial has been registered and allocated with the Australian New Zealand Clinical Trials Registry (ANZCTR) on 17/10/2012 with reference number ACTRN12612001111864.,There were no significant baseline differences between treatment groups.,With ICS, vessels and angiogenic factors did not change in hypervascular reticular basement membrane, but in the hypovascular lamina propria (LP), vessels increased and this had a proportionate effect on lung air trapping.,There was modest evidence for a reduction in LP vessels staining for VEGF with ICS treatment, but a marked and significant reduction in p-SMAD 2/3 expression.,Six-month high-dose ICS treatment had little effect on hypervascularity or angiogenic growth factors in the reticular basement membrane in COPD, but normalized hypovascularity in the LP, and this was physiologically relevant, though accompanied by a paradoxical reduction in growth factor expression. | Chronic obstructive pulmonary disease (COPD) has seriously impacted the health of individuals and populations.,In this study, proton nuclear magnetic resonance (1H NMR)-based metabonomics combined with multivariate pattern recognition analysis was applied to investigate the metabolic signatures of patients with COPD.,Serum and urine samples were collected from COPD patients (n = 32) and healthy controls (n = 21), respectively.,Samples were analyzed by high resolution 1H NMR (600 MHz), and the obtained spectral profiles were then subjected to multivariate data analysis.,Consistent metabolic differences have been found in serum as well as in urine samples from COPD patients and healthy controls.,Compared to healthy controls, COPD patients displayed decreased lipoprotein and amino acids, including branched-chain amino acids (BCAAs), and increased glycerolphosphocholine in serum.,Moreover, metabolic differences in urine were more significant than in serum.,Decreased urinary 1-methylnicotinamide, creatinine and lactate have been discovered in COPD patients in comparison with healthy controls.,Conversely, acetate, ketone bodies, carnosine, m-hydroxyphenylacetate, phenylacetyglycine, pyruvate and α-ketoglutarate exhibited enhanced expression levels in COPD patients relative to healthy subjects.,Our results illustrate the potential application of NMR-based metabonomics in early diagnosis and understanding the mechanisms of COPD. | 1 |
The latest chronic obstructive pulmonary disease (COPD) epidemiology survey in China estimated that there were 99 million potential COPD patients in the country, the majority of whom are undiagnosed.,Screening for COPD in primary care settings is of vital importance for China, but it is not known which strategy would be the most suitable for adoption in primary care.,Studies have been conducted to test the accuracy of questionnaires, expiratory peak flow meters and microspirometers to screen for COPD, but no study has directly evaluated and compared the effectiveness and cost-effectiveness of these methods in the Chinese setting.,We present the protocol for a multicentre cross-sectional study, to be conducted in eight community hospitals from four cities among Chinese adults aged 40 years or older to investigate the effectiveness and cost-effectiveness of different case-finding methods for COPD, and determine the test performance of individual and combinations of screening tests and strategies in comparison with quality diagnostic spirometry.,Index tests are screening questionnaires (COPD Diagnostic Questionnaire (CDQ), COPD Assessment in Primary Care To Identify Undiagnosed Respiratory Disease and Exacerbation Risk Questionnaire (CAPTURE), symptom-based questionnaire, COPD Screening Questionnaire (COPD-SQ)), microspirometer and peak flow.,Each participant will complete all of these tests in one assessment.,The primary analysis will compare the performance of a screening questionnaire with a handheld device.,Secondary analyses will include the comparative performance of each index test, as well as a comparison of strategies where we use a screening questionnaire and a handheld device.,Approximately 2000 participants will be recruited over 9 to 12 months.,The study has been approved by Peking University Hospital and University of Birmingham.,All study participants will provide written informed consent.,Study results will be published in appropriate journal and presented at national and international conferences, as well as relevant social media and various community/stakeholder engagement activities.,ISRCTN13357135. | Chronic obstructive pulmonary disease (COPD) and asthma are common diseases with a heterogeneous distribution worldwide.,Here, we present methods and disease and risk estimates for COPD and asthma from the Global Burden of Diseases, Injuries, and Risk Factors (GBD) 2015 study.,The GBD study provides annual updates on estimates of deaths, prevalence, and disability-adjusted life years (DALYs), a summary measure of fatal and non-fatal disease outcomes, for over 300 diseases and injuries, for 188 countries from 1990 to the most recent year.,We estimated numbers of deaths due to COPD and asthma using the GBD Cause of Death Ensemble modelling (CODEm) tool.,First, we analysed data from vital registration and verbal autopsy for the aggregate category of all chronic respiratory diseases.,Subsequently, models were run for asthma and COPD relying on covariates to predict rates in countries that have incomplete or no vital registration data.,Disease estimates for COPD and asthma were based on systematic reviews of published papers, unpublished reports, surveys, and health service encounter data from the USA.,We used the Global Initiative of Chronic Obstructive Lung Disease spirometry-based definition as the reference for COPD and a reported diagnosis of asthma with current wheeze as the definition of asthma.,We used a Bayesian meta-regression tool, DisMod-MR 2.1, to derive estimates of prevalence and incidence.,We estimated population-attributable fractions for risk factors for COPD and asthma from exposure data, relative risks, and a theoretical minimum exposure level.,Results were stratified by Socio-demographic Index (SDI), a composite measure of income per capita, mean years of education over the age of 15 years, and total fertility rate.,In 2015, 3·2 million people (95% uncertainty interval [UI] 3·1 million to 3·3 million) died from COPD worldwide, an increase of 11·6% (95% UI 5·3 to 19·8) compared with 1990.,There was a decrease in age-standardised death rate of 41·9% (37·7 to 45·1) but this was counteracted by population growth and ageing of the global population.,From 1990 to 2015, the prevalence of COPD increased by 44·2% (41·7 to 46·6), whereas age-standardised prevalence decreased by 14·7% (13·5 to 15·9).,In 2015, 0·40 million people (0·36 million to 0·44 million) died from asthma, a decrease of 26·7% (−7·2 to 43·7) from 1990, and the age-standardised death rate decreased by 58·8% (39·0 to 69·0).,The prevalence of asthma increased by 12·6% (9·0 to 16·4), whereas the age-standardised prevalence decreased by 17·7% (15·1 to 19·9).,Age-standardised DALY rates due to COPD increased until the middle range of the SDI before reducing sharply.,Age-standardised DALY rates due to asthma in both sexes decreased monotonically with rising SDI.,The relation between with SDI and DALY rates due to asthma was attributed to variation in years of life lost (YLLs), whereas DALY rates due to COPD varied similarly for YLLs and years lived with disability across the SDI continuum.,Smoking and ambient particulate matter were the main risk factors for COPD followed by household air pollution, occupational particulates, ozone, and secondhand smoke.,Together, these risks explained 73·3% (95% UI 65·8 to 80·1) of DALYs due to COPD.,Smoking and occupational asthmagens were the only risks quantified for asthma in GBD, accounting for 16·5% (14·6 to 18·7) of DALYs due to asthma.,Asthma was the most prevalent chronic respiratory disease worldwide in 2015, with twice the number of cases of COPD.,Deaths from COPD were eight times more common than deaths from asthma.,In 2015, COPD caused 2·6% of global DALYs and asthma 1·1% of global DALYs.,Although there are laudable international collaborative efforts to make surveys of asthma and COPD more comparable, no consensus exists on case definitions and how to measure disease severity for population health measurements like GBD.,Comparisons between countries and over time are important, as much of the chronic respiratory burden is either preventable or treatable with affordable interventions.,Bill & Melinda Gates Foundation. | 1 |
Despite the availability of guideline recommendations, diagnostic confusion between COPD and asthma appears common, and often it is very difficult to decide whether the obstruction is caused by asthma or COPD in a patient with airway obstruction.,However, there are well-defined features that help in differentiating asthma from COPD in the presence of fixed airflow obstruction.,Nonetheless, the presentations of asthma and COPD can converge and mimic each other, making it difficult to give these patients a diagnosis of either condition.,The association of asthma and COPD in the same patient has been designated mixed asthma-COPD phenotype or overlap syndrome.,However, since the absence of a clear definition and the inclusion of patients with different characteristics under this umbrella term, it may not facilitate treatment decisions, especially in the absence of clinical trials addressing this heterogeneous population.,We are realizing that neither asthma nor COPD are single diseases, but rather syndromes consisting of several endotypes and phenotypes, consequently comprising a spectrum of diseases that must be recognized and adequately treated with targeted therapy.,Therefore, we must treat patients by personalizing therapy on the basis of those treatable traits present in each subject. | Female smokers have increased risk of chronic obstructive pulmonary disease (COPD) compared with male smokers who have a similar history of cigarette smoke exposure.,We have shown previously that chronic smoke exposure for 6 months leads to increased airway wall remodeling in female C57BL/6 mice compared with male C57BL/6 mice.,These differences, however, were not evident in female ovariectomized mice exposed to cigarette smoke.,Herein, we report on the pulmonary function test results from the flexiVent system, which was used to determine the potential functional consequences of the histologic changes observed in these mice.,We found that tissue damping (G) was increased in female compared to male or ovariectomized female mice after smoke exposure.,At low oscillating frequencies, complex input resistance (Zrs) and impedance (Xrs) of the respiratory system was increased and decreased, respectively, in female but not in male or ovariectomized female mice after smoke exposure.,Quasistatic pressure-volume curves revealed a reduction in inspiratory capacity in female mice but not in male or ovariectomized female mice after smoke exposure.,The remaining lung function measurements including quasistatic compliance were similar amongst all groups.,This is the first study characterizing a sexual dimorphism in respiratory functional properties in a mouse model of COPD.,These findings demonstrate that increased airway remodeling in female mice following chronic smoke exposure is associated with increased tissue resistance in the peripheral airways.,These data may explain the importance of female sex hormones and the increased risk of airway disease in female smokers. | 1 |
Short-acting β2-agonist (SABA) bronchodilators help alleviate symptoms in chronic obstructive pulmonary disease (COPD) and may be a useful marker of symptom severity.,This analysis investigated whether SABA use impacts treatment differences between maintenance dual- and mono-bronchodilators in patients with COPD.,The Early MAXimisation of bronchodilation for improving COPD stability (EMAX) trial randomised symptomatic patients with low exacerbation risk not receiving inhaled corticosteroids 1:1:1 to once-daily umeclidinium/vilanterol 62.5/25 μg, once-daily umeclidinium 62.5 μg or twice-daily salmeterol 50 μg for 24 weeks.,Pre-specified subgroup analyses stratified patients by median baseline SABA use (low, < 1.5 puffs/day; high, ≥1.5 puffs/day) to examine change from baseline in trough forced expiratory volume in 1 s (FEV1), change in symptoms (Transition Dyspnoea Index [TDI], Evaluating Respiratory Symptoms-COPD [E-RS]), daily SABA use and exacerbation risk.,A post hoc analysis used fractional polynomial modelling with continuous transformations of baseline SABA use covariates.,At baseline, patients in the high SABA use subgroup (mean: 3.91 puffs/day, n = 1212) had more severe airflow limitation, were more symptomatic and had worse health status versus patients in the low SABA use subgroup (0.39 puffs/day, n = 1206).,Patients treated with umeclidinium/vilanterol versus umeclidinium demonstrated statistically significant improvements in trough FEV1 at Week 24 in both SABA subgroups (59-74 mL; p < 0.001); however, only low SABA users demonstrated significant improvements in TDI (high: 0.27 [p = 0.241]; low: 0.49 [p = 0.025]) and E-RS (high: 0.48 [p = 0.138]; low: 0.60 [p = 0.034]) scores.,By contrast, significant reductions in mean SABA puffs/day with umeclidinium/vilanterol versus umeclidinium were observed only in high SABA users (high: − 0.56 [p < 0.001]; low: − 0.10 [p = 0.132]).,Similar findings were observed when comparing umeclidinium/vilanterol and salmeterol.,Fractional polynomial modelling showed baseline SABA use ≥4 puffs/day resulted in smaller incremental symptom improvements with umeclidinium/vilanterol versus umeclidinium compared with baseline SABA use < 4 puffs/day.,In high SABA users, there may be a smaller difference in treatment response between dual- and mono-bronchodilator therapy; the reasons for this require further investigation.,SABA use may be a confounding factor in bronchodilator trials and in high SABA users; changes in SABA use may be considered a robust symptom outcome.,GlaxoSmithKline (study number 201749 [NCT03034915]). | This study evaluated the efficacy of tiotropium/olodaterol vs tiotropium on lung function, exercise capacity, and physical activity in patients with COPD.,A total of 184 patients aged ≥40 years with COPD (Global Initiative for Chronic Obstructive Lung Disease stage II-IV) received tiotropium/olodaterol for 6 weeks, then tiotropium for 6 weeks, or vice versa.,The primary endpoint was inspiratory capacity (IC) at peak post-dose.,Adjusted mean IC after 6-week treatment was 1.990 L with tiotropium/olodaterol vs 1.875 L with tiotropium (difference: 115 mL; 95% CI: 77, 153; p<0.0001).,Forced expiratory volume in 1 s (difference: 105 mL; 95% CI: 88, 123), forced vital capacity (difference: 163 mL; 95% CI: 130, 197), and slow vital capacity (difference: 134 mL; 95% CI: 91, 176) improved with tiotropium/olodaterol (all p<0.0001).,Adjusted mean 6-min walk distance was similar between treatments in the overall population but was significantly increased with tiotropium/olodaterol in the subgroup with Global Initiative for Chronic Obstructive Lung Disease stage III/IV at baseline (difference: 18.1 m; 95% CI: 2.3, 33.9; p=0.0254).,In a post hoc analysis, tiotropium/olodaterol improved the values for ≥2.0 metabolic equivalents (difference: 5.0 min; 95% CI: 0.4, 9.7; p=0.0337).,Tiotropium/olodaterol significantly improved IC compared with tiotropium and potentially enhanced the exercise capacity in COPD patients.,A slight improvement in physical activity of relatively more than moderate intensity was also seen with tiotropium/olodaterol. | 1 |
Efficacy and safety of tiotropium+olodaterol fixed-dose combination (FDC) compared with the mono-components was evaluated in patients with moderate to very severe chronic obstructive pulmonary disease (COPD) in two replicate, randomised, double-blind, parallel-group, multicentre, phase III trials.,Patients received tiotropium+olodaterol FDC 2.5/5 μg or 5/5 μg, tiotropium 2.5 μg or 5 μg, or olodaterol 5 μg delivered once-daily via Respimat inhaler over 52 weeks.,Primary end points were forced expiratory volume in 1 s (FEV1) area under the curve from 0 to 3 h (AUC0-3) response, trough FEV1 response and St George's Respiratory Questionnaire (SGRQ) total score at 24 weeks.,In total, 5162 patients (2624 in Study 1237.5 and 2538 in Study 1237.6) received treatment.,Both FDCs significantly improved FEV1 AUC0-3 and trough FEV1 response versus the mono-components in both studies.,Statistically significant improvements in SGRQ total score versus the mono-components were only seen for tiotropium+olodaterol FDC 5/5 μg.,Incidence of adverse events was comparable between the FDCs and the mono-components.,These studies demonstrated significant improvements in lung function and health-related quality of life with once-daily tiotropium+olodaterol FDC versus mono-components over 1 year in patients with moderate to very severe COPD.,Lung function and symptomatic benefits of daily tiotropium+olodaterol fixed-dose combination in moderate to very severe COPDhttp://ow.ly/DIKiY | Few studies have investigated the 24-hour symptom profile in patients with COPD or how symptoms during the 24-hour day are inter-related.,This observational study assessed the prevalence, severity and relationship between night-time, early morning and daytime COPD symptoms and explored the relationship between 24-hour symptoms and other patient-reported outcomes.,The study enrolled patients with stable COPD in clinical practice.,Baseline night-time, early morning and daytime symptoms (symptom questionnaire), severity of airflow obstruction (FEV1), dyspnoea (modified Medical Research Council Dyspnoea Scale), health status (COPD Assessment Test), anxiety and depression levels (Hospital Anxiety and Depression Scale), sleep quality (COPD and Asthma Sleep Impact Scale) and physical activity level (sedentary, moderately active or active) were recorded.,The full analysis set included 727 patients: 65.8% male, mean ± standard deviation age 67.2 ± 8.8 years, % predicted FEV1 52.8 ± 20.5%.,In each part of the 24-hour day, >60% of patients reported experiencing ≥1 symptom in the week before baseline.,Symptoms were more common in the early morning and daytime versus night-time (81.4%, 82.7% and 63.0%, respectively).,Symptom severity was comparable for each period assessed.,Overall, in the week before baseline, 56.7% of patients had symptoms throughout the whole 24-hour day (3 parts of the day); 79.9% had symptoms in ≥2 parts of the 24-hour day.,Symptoms during each part of the day were inter-related, irrespective of disease severity (all p < 0.001).,Early morning and daytime symptoms were associated with the severity of airflow obstruction (p < 0.05 for both).,Night-time, early morning and daytime symptoms were all associated with worse dyspnoea, health status and sleep quality, and higher anxiety and depression levels (all p < 0.001 versus patients without symptoms in each corresponding period).,In each part of the 24-hour day, there was also an association between symptoms and a patient’s physical activity level (p < 0.05 for each period).,More than half of patients experienced COPD symptoms throughout the whole 24-hour day.,There was a significant relationship between night-time, early morning and daytime symptoms.,In each period, symptoms were associated with worse patient-reported outcomes, suggesting that improving 24-hour symptoms should be an important consideration in the management of COPD.,The online version of this article (doi:10.1186/s12931-014-0122-1) contains supplementary material, which is available to authorized users. | 1 |
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